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Korukire N, Godson A, Mukamurigo J, de Dieu Habimana J, Josias I, Ntakirutimana T. Effects of indoor air pollution exposure on lung function of children in selected schools in Kigali, Rwanda. Sci Rep 2025; 15:13617. [PMID: 40253459 PMCID: PMC12009278 DOI: 10.1038/s41598-025-92047-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 02/25/2025] [Indexed: 04/21/2025] Open
Abstract
Exposure to particulate matter (PM) in schools significantly contributes to respiratory problems among children found in such learning environments. There is limited information about the health effects of exposure to PM in schools in Rwanda. The aim of this study was to assess the adverse effects of PM on children's lung function in selected schools in Kigali, Rwanda. The study was conducted in six public primary schools classified as highly or moderately exposed schools based on their proximity to pollution sources. The study involved 107 randomly selected children aged 8 to 15. The study measured the indoor air concentrations of PM2.5 and PM10 and tested the lung function of school children. Three lung function indicators including forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and peak expiratory flow (PEF) were measured. Both forms of data were collected during the dry and rainy seasons. Air quality was monitored in classrooms using Purple Air PA-II sensors, and the children's lung function was measured using a spirometer. Linear regression analysis was used to determine the associations between PM2.5 and PM10 concentrations and lung function at p = 0.05. The findings showed that the concentrations of PM2.5 were two to five times higher, and PM10 levels were about two times higher than the World Health Organization's air quality guidelines. Both PM2.5 and PM10 were associated with reduced lung function, regardless of the season. The present study shows significant adverse effects of exposure to PM10 and PM2.5 on the lung function of children in the selected schools. Hence there is the need to take measures to improve air quality and protect the health of school communities.
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Affiliation(s)
- Noel Korukire
- Department of Environmental Health Sciences, University of Rwanda, Kigali, Rwanda.
| | - Ana Godson
- Department of Environmental Health Sciences, University of Ibadan, Ibadan, Nigeria
| | - Judith Mukamurigo
- Department of Epidemiology and Biostatistics, University of Rwanda, Kigali, Rwanda
| | | | - Izabayo Josias
- Department of Epidemiology and Disease Control, Mount Kigali University, Kigali, Rwanda
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Chen J, Xu J, Li L, Yuan Y, Jiang J, Sun Y. Propofol regulates the progression of hepatocellular carcinoma via the POLR2L/TGF-β signaling pathway. Transl Cancer Res 2024; 13:2266-2281. [PMID: 38881942 PMCID: PMC11170526 DOI: 10.21037/tcr-23-2066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 04/11/2024] [Indexed: 06/18/2024]
Abstract
Background Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Propofol has been reported to modulate tumorigenesis in HCC; the aim of this study was to investigate the effect of the interaction of propofol with POLR2L on HCC tumor progression in HCC. Methods The propofol-related GSE101724 dataset was analyzed using weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify overlapping genes. Key genes were selected from The Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC)-DEGs for prognostic analysis. The impact of POLR2L on LIHC patient survival was assessed, followed by in vitro experiments to validated its effects on HCC cell behavior and signaling pathways. Results Fourteen overlapping genes were identified in the turquoise module (highest correlation) of up-regulated DEGs and GSE101724. Further analysis obtained 11 key overlapping genes from 14 overlapping genes and TCGA-LIHC-DEGs, among which HSPE1 and POLR2L showed significant prognostic correlation. Patients with LIHC have a worse chance of surviving when their POLR2L expression is elevated. Knockdown POLR2L significantly inhibited the proliferation, invasion, and migration of HCC cell lines. Downregulation of POLR2L was accompanied by induced apoptosis, cell cycle arrest, and modulation of the expression of apoptosis-related genes. Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth. Further, it was shown that propofol controlled the development of HCC by influencing the POLR2L/TGF-β signaling loop. Conclusions The results validated the predictive relevance of POLR2L in HCC and emphasized that propofol can regulate HCC progression through the POLR2L/TGF-β signaling pathway.
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Affiliation(s)
- Jiaying Chen
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Jing Xu
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Lei Li
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Yawei Yuan
- Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jun Jiang
- School of Life Sciences, Fudan University, Shanghai, China
| | - Yuming Sun
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
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Zhang W, Liu J, Li X, Bai Z, Sun Y, Chen X. Lidocaine effects on neutrophil extracellular trapping and angiogenesis biomarkers in postoperative breast cancer patients with different anesthesia methods: a prospective, randomized trial. BMC Anesthesiol 2024; 24:162. [PMID: 38678209 PMCID: PMC11055234 DOI: 10.1186/s12871-024-02540-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 04/11/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Anesthesia techniques and drug selection may influence tumor recurrence and metastasis. Neutrophil extracellular trapping (NETosis), an immunological process, has been linked to an increased susceptibility to metastasis in individuals with tumors. Furthermore, recurrence may be associated with vascular endothelial growth factor A (VEGF-A), a mediator of angiogenesis. This study investigates the impact of lidocaine (combined with sevoflurane or propofol anesthesia ) during breast cancer surgery inhibits the expression of biomarkers associated with metastasis and recurrence (specifically H3Cit, NE, MPO, MMP-9 and VEGF-A). METHODS We randomly assigned 120 women undergoing primary or invasive breast tumor resection to receive one of four anesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Blood samples were collected before induction and 3 h after the operation. Biomarkers associated with NETosis (citrullinated histone H3 [H3Cit], myeloperoxidase [MPO], and neutrophil elastase [NE]) and angiogenesis were quantified using enzyme-linked immunosorbent assays. RESULTS Patient and breast tumor characteristics, along with perioperative management, did not differ between study groups. In intra-group comparisons, S and P groups demonstrated a statistically significant increase in post-operative MPO (S group: 10.39[6.89-17.22] vs. 14.31[8.55-20.87] ng ml-1, P = 0.032; P group: 9.45[6.73-17.37] vs. 14.34[9.87-19.75] ng ml-1, P = 0.035)and NE(S group: 182.70[85.66-285.85] vs. 226.20[91.85-391.65] ng ml-1, P = 0.045; P group: 154.22[97.31-325.30] vs. 308.66[132.36-483.57] ng ml-1, P = 0.037) concentrations compared to pre-operative measurements, whereas SL and PL groups did not display a similar increase. H3Cit, MMP-9, and VEGF-A concentrations were not significantly influenced by the anesthesia techniques and drugs. CONCLUSIONS Regardless of the specific technique employed for general anesthesia, there was no increase in the postoperative serum concentrations of MPO and NE after perioperative lidocaine infusion compared to preoperative serum concentrations. This supports the hypothesis that intravenous lidocaine during cancer surgery aimed at achieving a cure may potentially decrease the likelihood of recurrence. Further interpretation and discussion of clinical implications are warranted, emphasizing the significance of these findings in the context of cancer surgery and recurrence prevention. CLINICAL TRIAL REGISTRATION ChiCTR2300068563.
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Affiliation(s)
- Wenjuan Zhang
- School of Clinical Medicine, Ningxia Medical University, No.692 Shengli South Street Xingqing District, Yinchuan, 750004, Ningxia, China
| | - Jiao Liu
- School of Clinical Medicine, Ningxia Medical University, No.692 Shengli South Street Xingqing District, Yinchuan, 750004, Ningxia, China
| | - Xiaohui Li
- Department of Anaesthesia and Perioperative Medicine, Cancer Hospital, General Hospital of Ningxia Medical University, No.804 Shengli South Street Xingqing District, Yinchuan, 750004, Ningxia, China
| | - Zhixia Bai
- Department of Anaesthesia and Perioperative Medicine, Cancer Hospital, General Hospital of Ningxia Medical University, No.804 Shengli South Street Xingqing District, Yinchuan, 750004, Ningxia, China
| | - Yan Sun
- Department of Anaesthesia and Perioperative Medicine, Cancer Hospital, General Hospital of Ningxia Medical University, No.804 Shengli South Street Xingqing District, Yinchuan, 750004, Ningxia, China
| | - Xuexin Chen
- Department of Anaesthesia and Perioperative Medicine, Cancer Hospital, General Hospital of Ningxia Medical University, No.804 Shengli South Street Xingqing District, Yinchuan, 750004, Ningxia, China.
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Wahdan-Alaswad RS, Edgerton SM, Kim HM, Tan AC, Haugen BR, Liu B, Thor AD. Thyroid hormone enhances estrogen-mediated proliferation and cell cycle regulatory pathways in steroid receptor-positive breast Cancer. Cell Cycle 2023:1-20. [PMID: 37723865 DOI: 10.1080/15384101.2023.2249702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 08/15/2023] [Indexed: 09/20/2023] Open
Abstract
Estrogen receptor (ER) α expression and associated signaling is a major driver of over two-thirds of all breast cancers (BC). ER targeting strategies are typically used as a first-line therapy in patients with steroid receptor positive (SR+) disease. Secondary resistance to anti-estrogenic agents may occur with clonal expansion and disease progression. Mechanisms underlying hormone resistance are an expanding field of significant translational importance. Cross-talk with other nuclear hormones, receptors, and signaling pathways, including thyroid hormones (TH) and their receptors (THRs), have been shown to promote endocrine therapy resistance in some studies. We have shown that TH replacement therapy (THRT) was independently and significantly associated with higher rates of relapse and mortality in SR positive (+), node-negative (LN-) BC patients, whereas it showed no association with outcomes in SR negative (-) patients. LN-, SR+ patients receiving THRT and tamoxifen had the worst outcomes, suggesting a pro-carcinogenic interaction that significantly and independently shortened survival and increased mortality. Using in vivo and in vitro models, we previously showed hormonal cross-talk, altered gene signaling, target gene activation, and resistance to tamoxifen in the presence of TH. In this report, we show TH ± E2 ± tamoxifen inhibits cell cycle control signaling, reduces apoptosis, and enhances cell proliferation, tumor growth, tamoxifen resistance, and clonal expansion. Mechanistically these changes involve numerous genes and pathways, including critical cell cycle regulatory proteins and genes identified using various molecular methods. These studies facilitate a greater mechanistic understanding of the biological and molecular impact of TH on SR+ BC.
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Affiliation(s)
- Reema S Wahdan-Alaswad
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- University of Colorado Cancer Center, Aurora, CO, USA
| | - Susan M Edgerton
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- University of Colorado Cancer Center, Aurora, CO, USA
| | - Hyun Min Kim
- Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA
| | - Aik Choon Tan
- Department of Oncological Sciences and Biomedical Informatics, Huntsman Cancer Institute, Salt Lake City, Utah, USA
| | - Bryan R Haugen
- University of Colorado Cancer Center, Aurora, CO, USA
- Division of Endocrinology, Metabolism, & Diabetes, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA
| | - Bolin Liu
- Department of Genetics, Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University (LSU) Health Sciences Center, New Orleans, LA, USA
| | - Ann D Thor
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- University of Colorado Cancer Center, Aurora, CO, USA
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Augimeri G, Bonofiglio D. Promising Effects of N-Docosahexaenoyl Ethanolamine in Breast Cancer: Molecular and Cellular Insights. Molecules 2023; 28:molecules28093694. [PMID: 37175104 PMCID: PMC10180201 DOI: 10.3390/molecules28093694] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/21/2023] [Accepted: 04/23/2023] [Indexed: 05/15/2023] Open
Abstract
Unhealthy dietary habits have been identified as a risk factor for the development and progression of cancer. Therefore, adopting a healthy eating pattern is currently recommended to prevent the onset of different types of cancers, including breast carcinoma. In particular, the Mediterranean diet, based on high consumption of omega-3 polyunsaturated fatty acids (N-3 PUFAs), such as those found in cold-water fish and other seafood, nuts, and seeds, is recommended to reduce the incidence of several chronic-degenerative diseases. Indeed, the consumption of N-3 PUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced the risk of different types of cancer, including breast cancer. Moreover, they can counteract breast cancer progression and reduce the side effects of chemotherapy in breast cancer survival. Studies have demonstrated that DHA, exhibiting greater antitumor activity than EPA in breast cancer, can be attributed to its direct impact on breast cancer cells and also due to its conversion into various metabolites. N-docosahexaenoyl ethanolamine, DHEA, is the most studied DHA derivative for its therapeutic potential in breast cancer. In this review, we emphasize the significance of dietary habits and the consumption of N-3 polyunsaturated fatty acids, particularly DHA, and we describe the current knowledge on the antitumoral action of DHA and its derivative DHEA in the treatment of breast cancer.
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Affiliation(s)
- Giuseppina Augimeri
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy
| | - Daniela Bonofiglio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy
- Centro Sanitario, University of Calabria, 87036 Rende, CS, Italy
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Propofol Suppresses Glioma Tumorigenesis by Regulating circ_0047688/miR-516b-5p/IFI30 Axis. Biochem Genet 2023; 61:151-169. [PMID: 35763173 DOI: 10.1007/s10528-022-10243-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 06/07/2022] [Indexed: 01/24/2023]
Abstract
Propofol has recently attracted increasing attention for its anti-tumor property in cancers, including glioma. Circular RNAs (circRNAs) can act as key regulators in various cancers. However, the relationship between propofol and circ_0047688 in glioma is still unclear. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays. Cell migration and invasion were determined using transwell assay. Cell apoptosis was detected by flow cytometry. Protein levels and RNA levels were detected by western blot assay and real-time quantitative polymerase chain reaction (RT‑qPCR), respectively. The intermolecular interaction was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. A mouse xenograft model was established for in vivo experiments. Propofol inhibited cell proliferation, migration, and invasion and accelerated apoptosis in glioma cells. Circ_0047688 was upregulated in glioma tissues and cells, and propofol downregulated circ_0047688 in a dose-dependent manner. Circ_0047688 knockdown inhibited glioma cell progression and its overexpression abated the anti-tumor role of propofol in glioma cells. Moreover, miR-516b-5p was a direct target of circ_0047688, and circ_0047688 promoted glioma cell progression by sponging miR-516b-5p. In addition, IFI30 was a direct target of miR-516b-5p, and miR-516b-5p inhibited glioma cell malignant behaviors by targeting IFI30 in propofol-treated cells. Furthermore, circ_0047688 overexpression could weaken the anti-tumor role of propofol in vivo. Propofol inhibited glioma progression via modulating circ_0047688/miR-516b-5p/IFI30 axis, providing a potential therapeutic strategy for treatment of glioma.
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Oh CS, Hong SW, Park S, Kwon Y, Kim SH. Effect of equipotent doses of propofol and sevoflurane on endoplasmic reticulum stress during breast cancer surgery. Korean J Anesthesiol 2022; 75:487-495. [PMID: 35760393 PMCID: PMC9726458 DOI: 10.4097/kja.21569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 06/27/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Numerous studies suggest that intravenous propofol is superior to inhaled volatile anesthetic. This study compared the changes in the endoplasmic reticulum (ER) stress of cancer cells and lymphocytes after propofol- and sevoflurane-based anesthesia during breast cancer surgery. METHODS We randomized 53 patients undergoing breast cancer surgery to propofol (n = 28) and sevoflurane (n = 25) anesthesia groups. Blood samples were obtained immediately before inducing anesthesia, and 1 and 24 h postoperatively. Human breast cancer cell lines were cultured and treated with patient plasma, and the frequency of C/EBP homologous protein (CHOP) on the cancer cell lines and lymphocytes was measured. The neutrophil-to-lymphocyte ratio in plasma was evaluated in both groups. RESULTS The CHOP expression on breast cancer cell lines did not differ between the groups (P = 0.108), although it decreased significantly over time (P = 0.027). The CHOP expression on lymphocytes was comparable between the groups (P = 0.485), and was the neutrophil-to-lymphocyte ratio (P = 0.501). CONCLUSIONS Propofol-based anesthesia did not induce greater ER stress than sevoflurane-based anesthesia during breast cancer surgery. The ER stress of cancer cells did not differ according to the type of anesthesia during breast cancer surgery.
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Affiliation(s)
- Chung-Sik Oh
- Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea,Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea
| | - Seung Wan Hong
- Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Sarah Park
- Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Yubi Kwon
- Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Seong-Hyop Kim
- Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea,Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea,Department of Infection and Immunology, Konkuk University School of Medicine, Seoul, Korea,Corresponding author: Seong-Hyop Kim, M.D., Ph.D Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, KoreaTel: +82-2-2030-5454Fax: +82-2-2030-5449 ;;
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Zhao H, Wu S, Luo Z, Liu H, Sun J, Jin X. The association between circulating docosahexaenoic acid and lung cancer: A Mendelian randomization study. Clin Nutr 2022; 41:2529-2536. [PMID: 36223714 DOI: 10.1016/j.clnu.2022.09.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 09/06/2022] [Accepted: 09/07/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Lung cancer is a malignant tumor with a high incidence, it is vital to identify modifiable and avoidable risk factors for primary prevention, which can significantly lower the risk of cancer by preventing exposure to hazards and altering risky behavior. Some observational studies suggest that an increase in docosahexaenoic acid (DHA) consumption can reduce lung cancer risk. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To evaluate the link between DHA and lung cancer, we have undertaken this analysis to examine the causal association between DHA and the risk of lung cancer using a two-sample Mendelian randomization (MR) framework. METHODS We performed a two-sample MR analysis to evaluate the causal effect of plasma DHA levels on lung cancer risk. For the exposure data, we extracted genetic variants as instrumental variables (IVs) that are strongly associated with DHA from a large-scale genome-wide association study (GWAS). We obtained the corresponding effect estimates for IVs on the risk of lung cancer with 11,348 cases and 15,861 controls. Finally, we applied Mendelian randomization analysis to obtain preliminary MR results and performed sensitivity analyses to verify the robustness of our results. RESULTS According to the primary MR estimates and further sensitivity analyses, a higher serum DHA level was associated with a higher risk of lung cancer [OR = 1.159, 95% CI (1.04-1.30), P = 0.01]. For lung adenocarcinoma, the results also showed a close correlation between the DHA level and lung adenocarcinoma [OR = 1.277, 95% CI (1.09-1.50), P = 0.003], but it was not statistically significant for squamous cell carcinoma [OR = 1.071, 95% CI (0.89-1.29), P = 0.467]. CONCLUSIONS Our study revealed that plasma DHA is positively associated with the risk of lung cancer overall, especially for lung adenocarcinoma. This study provides new information to develop dietary guidelines for primary lung cancer prevention.
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Affiliation(s)
- Hang Zhao
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China; China-Japan Friendship Hospital, Yinghuadong Road, Beijing 100029, Chaoyang District, China
| | - Shengnan Wu
- The First Affiliated Hospital of China Medical University, Shengyang, China
| | - Zhenkai Luo
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hailong Liu
- Department of Joint Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou Guangdong, China
| | - Junwei Sun
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China
| | - Xiaolin Jin
- The First Affiliated Hospital of China Medical University, Shengyang, China; Department of International Physical Examination Center, The First Affiliated Hospital of China Medical University, Shengyang, China.
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Jiang T, Xie L, Zhou S, Liu Y, Huang Y, Mei N, Ma F, Gong J, Gao X, Chen J. Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment. J Nanobiotechnology 2022; 20:394. [PMID: 36045429 PMCID: PMC9429706 DOI: 10.1186/s12951-022-01592-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/08/2022] [Indexed: 11/24/2022] Open
Abstract
Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy.
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Affiliation(s)
- Tianze Jiang
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China.,Key Laboratory of Marine Drugs, Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, People's Republic of China
| | - Laozhi Xie
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China
| | - Songlei Zhou
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China
| | - Yipu Liu
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China
| | - Yukun Huang
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China.,Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, People's Republic of China
| | - Ni Mei
- Shanghai Center for Drug Evaluation and Inspection, Lane 58, HaiQv Road, Shanghai, 201210, People's Republic of China
| | - Fenfen Ma
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China.,Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai, 201399, People's Republic of China
| | - Jingru Gong
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China. .,Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai, 201399, People's Republic of China.
| | - Xiaoling Gao
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, People's Republic of China.
| | - Jun Chen
- Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China. .,Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China.
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Bimonte S, Cascella M, Forte CA, Esposito G, Del Prato F, Raiano N, Del Prete P, Cuomo A. Effects of the Hypnotic Alkylphenol Derivative Propofol on Breast Cancer Progression. A Focus on Preclinical and Clinical Studies. In Vivo 2021; 35:2513-2519. [PMID: 34410937 PMCID: PMC8408744 DOI: 10.21873/invivo.12532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/31/2021] [Accepted: 06/03/2021] [Indexed: 11/10/2022]
Abstract
Propofol is a hypnotic alkylphenol derivative with many biological activities. It is predominantly used in anesthesia and is the most used parenteral anesthetic agent in the United States. Accumulating preclinical studies have shown that this compound may inhibit cancer recurrence and metastasis. Nevertheless, other investigations provided evidence that this compound may promote breast cancer cell progression by modulating different molecular pathways. Clinical data on this topic are scarce and derive from retrospective analyses. For this reason, we reviewed and evaluated the available data to reveal insight into this controversial issue. More preclinical and clinical investigations are necessary to determine the potential role of propofol in the proliferation of breast cancer cells.
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Affiliation(s)
- Sabrina Bimonte
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy;
| | - Marco Cascella
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Cira Antonietta Forte
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Gennaro Esposito
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Francesco Del Prato
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Nicola Raiano
- Radiology Division, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Via Mariano Semmola, Naples, Italy
| | - Paola Del Prete
- Direzione Scientifica, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Arturo Cuomo
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
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Tan SH, Ding HJ, Mei XP, Liu JT, Tang YX, Li Y. Propofol suppressed cell proliferation and enhanced apoptosis of bladder cancer cells by regulating the miR-340/CDK2 signal axis. Acta Histochem 2021; 123:151728. [PMID: 34048990 DOI: 10.1016/j.acthis.2021.151728] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/06/2021] [Accepted: 05/07/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND As widely reported, propofol can effectively inhibit tumors development. However, little is known about the molecular mechanisms. Here, we proved that propofol regulated miR-340/CDK2 axis to suppress bladder cancer progression in vitro. METHODS MicroRNA (MiR)-340 expression in 5637 cells was examined using qRT-PCR. Cyclin-dependent kinase2 (CDK2) expression was detected using both qRT-PCR and western blot. The levels of apoptosis-related proteins and cell cycle-related proteins were evaluated using western blot. CCK-8 assay and BrdU assay were conducted to evaluate cell proliferation. Moreover, flow cytometry assay was employed to assess cell cycle and cell apoptosis. Finally, dual luciferase reporter assay was employed to verify the binding relationship between miR-340 and CDK2. RESULTS Here we showed that propofol treatment inhibited cell proliferation of 5637 cells but enhanced cell apoptosis. Propofol upregulated miR-340 in a dose and time dependent manner. MiR-340 inhibitor could reverse the effect of propofol on the proliferation and apoptosis of 5637 cells. Next, dual luciferase reporter assay displayed that miR-340 directly bound to the 3'-UTR of CDK2. Finally, inhibition of CDK2 could partly reversed the effect of miR-340 inhibitor on cell proliferation and cell apoptosis of propofol-treated 5637 cells. CONCLUSION In total, our results proved that targeting miR340/CDK2 axis was novel to enhance the anti-tumor effects of propofol in bladder cancer in vitro, and our study provided alternative therapeutic strategies for clinical treatment of bladder cancer.
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Abstract
PURPOSE OF REVIEW Surgery remains integral to treating solid cancers. However, the surgical stress response, characterized by physiologic perturbation of the adrenergic, inflammatory, and immune systems, may promote procancerous pathways. Anesthetic technique per se may attenuate/enhance these pathways and thereby could be implicated in long-term cancer outcomes. RECENT FINDINGS To date, clinical studies have predominantly been retrospective and underpowered and, thus limit meaningful conclusions. More recently, prospective studies of regional anesthesia for breast and colorectal cancer surgery have failed to demonstrate long-term cancer outcome benefit. However, based on the consistent observation of protumorigenic effects of surgical stress and that of volatile anesthesia in preclinical studies, supported by in vivo models of tumor progression and metastasis, we await robust prospective clinical studies exploring the role of propofol-based total intravenous anesthesia (cf. inhalational volatiles). Additionally, anti-adrenergic/anti-inflammatory adjuncts, such as lidocaine, nonsteroidal anti-inflammatory drugs and the anti-adrenergic propranolol warrant ongoing research. SUMMARY The biologic perturbation of the perioperative period, compounded by the effects of anesthetic agents, renders patients with cancer particularly vulnerable to enhanced viability of minimal residual disease, with long-term outcome consequences. However, low level and often conflicting clinical evidence equipoise currently exists with regards to optimal oncoanesthesia techniques. Large, prospective, randomized control trials are urgently needed to inform evidence-based clinical practice guidelines.
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Choromańska A, Chwiłkowska A, Kulbacka J, Baczyńska D, Rembiałkowska N, Szewczyk A, Michel O, Gajewska-Naryniecka A, Przystupski D, Saczko J. Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy. Molecules 2021; 26:1850. [PMID: 33806009 PMCID: PMC8037978 DOI: 10.3390/molecules26071850] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/18/2021] [Accepted: 03/23/2021] [Indexed: 12/11/2022] Open
Abstract
Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols.
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Affiliation(s)
- Anna Choromańska
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Agnieszka Chwiłkowska
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Julita Kulbacka
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Dagmara Baczyńska
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Nina Rembiałkowska
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Anna Szewczyk
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Olga Michel
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Agnieszka Gajewska-Naryniecka
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
| | - Dawid Przystupski
- Department of Paediatric Bone Marrow Transplantation, Oncology and Haematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Jolanta Saczko
- Department of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; (J.K.); (D.B.); (N.R.); (A.S.); (O.M.); (A.G.-N.); (J.S.)
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Yu S, Xin W, Jiang Q, Li A. Propofol exerts neuroprotective functions by down-regulating microRNA-19a in glutamic acid-induced PC12 cells. Biofactors 2020; 46:934-942. [PMID: 31913544 DOI: 10.1002/biof.1607] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 12/17/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Propofol, a kind of intravenous sedative drug, is certified that exerts anti-inflammation and antitumor functions. However, the influence of propofol in cerebral injury and the corresponding mechanism remains unexplained, that our article focuses on. METHODS PC12 cells were treated with propofol and exposed in glutamic acid (Glu) solutions. Cell viability, apoptotic potential, apoptosis-related and autophagy-linked proteins were tested via CCK-8, flow cytometry, and western blot assays. Reverse transcription-quantitative real-time PCR was utilized to test miR-19a expression in Glu-stimulated cells. Next, miR-19a mimic transfection was used to assess the effects of miR-19a on cell apoptosis and autophagy in Glu or propofol treated cells. Finally, western blot was performed to test AMPK and mTOR pathways. RESULTS Glu exposure promoted cell apoptosis and autophagy of PC12 cells, while propofol attenuated cell apoptosis and autophagy triggered by Glu. Additionally, propofol decreased the miR-19a expression in Glu-stimulated PC12 cells. Meanwhile, over-expression of miR-19a reversed the effects of propofol on Glu-induced cell apoptosis and autophagy. Moreover, propofol potentiated AMPK and mTOR pathways in Glu-stimulated PC12 cells via impeding miR-19a expression. CONCLUSIONS These finding revealed that propofol relieved Glu-triggered apoptosis and autophagy of PC12, and activated AMPK and mTOR pathways by suppressing miR-19a expression.
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Affiliation(s)
- Shashuang Yu
- Department of Anesthesiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Wenqi Xin
- Department of Anesthesiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Qiliang Jiang
- Department of Anesthesiology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Aixiang Li
- Department of Anesthesiology, Huaihe Hospital of Henan University, Kaifeng, China
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Fattahi N, Shahbazi MA, Maleki A, Hamidi M, Ramazani A, Santos HA. Emerging insights on drug delivery by fatty acid mediated synthesis of lipophilic prodrugs as novel nanomedicines. J Control Release 2020; 326:556-598. [PMID: 32726650 DOI: 10.1016/j.jconrel.2020.07.012] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 07/09/2020] [Accepted: 07/10/2020] [Indexed: 12/25/2022]
Abstract
Many drug molecules that are currently in the market suffer from short half-life, poor absorption, low specificity, rapid degradation, and resistance development. The design and development of lipophilic prodrugs can provide numerous benefits to overcome these challenges. Fatty acids (FAs), which are lipophilic biomolecules constituted of essential components of the living cells, carry out many necessary functions required for the development of efficient prodrugs. Chemical conjugation of FAs to drug molecules may change their pharmacodynamics/pharmacokinetics in vivo and even their toxicity profile. Well-designed FA-based prodrugs can also present other benefits, such as improved oral bioavailability, promoted tumor targeting efficiency, controlled drug release, and enhanced cellular penetration, leading to improved therapeutic efficacy. In this review, we discuss diverse drug molecules conjugated to various unsaturated FAs. Furthermore, various drug-FA conjugates loaded into various nanostructure delivery systems, including liposomes, solid lipid nanoparticles, emulsions, nano-assemblies, micelles, and polymeric nanoparticles, are reviewed. The present review aims to inspire readers to explore new avenues in prodrug design based on the various FAs with or without nanostructured delivery systems.
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Affiliation(s)
- Nadia Fattahi
- Department of Chemistry, Faculty of Science, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran; Trita Nanomedicine Research Center (TNRC), Trita Third Millennium Pharmaceuticals, 45331-55681 Zanjan, Iran
| | - Mohammad-Ali Shahbazi
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Aziz Maleki
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehrdad Hamidi
- Trita Nanomedicine Research Center (TNRC), Trita Third Millennium Pharmaceuticals, 45331-55681 Zanjan, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Ali Ramazani
- Department of Chemistry, Faculty of Science, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran; Research Institute of Modern Biological Techniques (RIMBT), University of Zanjan, P.O. Box 45195-313, Zanjan, Iran
| | - Hélder A Santos
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland; Helsinki Institute of Life Science (HiLIFE), Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
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n-3 Polyunsaturated Fatty Acid Amides: New Avenues in the Prevention and Treatment of Breast Cancer. Int J Mol Sci 2020; 21:ijms21072279. [PMID: 32224850 PMCID: PMC7178041 DOI: 10.3390/ijms21072279] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 12/24/2022] Open
Abstract
Over the last decades a renewed interest in n−3 very long polyunsaturated fatty acids (PUFAs), derived mainly from fish oils in the human diet, has been observed because of their potential effects against cancer diseases, including breast carcinoma. These n−3 PUFAs mainly consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that, alone or in combination with anticancer agents, induce cell cycle arrest, autophagy, apoptosis, and tumor growth inhibition. A large number of molecular targets of n−3 PUFAs have been identified and multiple mechanisms appear to underlie their antineoplastic activities. Evidence exists that EPA and DHA also elicit anticancer effects by the conversion to their corresponding ethanolamide derivatives in cancer cells, by binding and activation of different receptors and distinct signaling pathways. Other conjugates with serotonin or dopamine have been found to exert anti-inflammatory activities in breast tumor microenvironment, indicating the importance of these compounds as modulators of tumor epithelial/stroma interplay. The objective of this review is to provide a general overview and an update of the current n−3 PUFA derivative research and to highlight intriguing aspects of the potential therapeutic benefits of these low-toxicity compounds in breast cancer treatment and care.
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Harnessing cancer immunotherapy during the unexploited immediate perioperative period. Nat Rev Clin Oncol 2020; 17:313-326. [PMID: 32066936 DOI: 10.1038/s41571-019-0319-9] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2019] [Indexed: 02/07/2023]
Abstract
The immediate perioperative period (days before and after surgery) is hypothesized to be crucial in determining long-term cancer outcomes: during this short period, numerous factors, including excess stress and inflammatory responses, tumour-cell shedding and pro-angiogenic and/or growth factors, might facilitate the progression of pre-existing micrometastases and the initiation of new metastases, while simultaneously jeopardizing immune control over residual malignant cells. Thus, application of anticancer immunotherapy during this critical time frame could potentially improve patient outcomes. Nevertheless, this strategy has rarely been implemented to date. In this Perspective, we discuss apparent contraindications for the perioperative use of cancer immunotherapy, suggest safe immunotherapeutic and other anti-metastatic approaches during this important time frame and specify desired characteristics of such interventions. These characteristics include a rapid onset of immune activation, avoidance of tumour-promoting effects, no or minimal increase in surgical risk, resilience to stress-related factors and minimal induction of stress responses. Pharmacological control of excess perioperative stress-inflammatory responses has been shown to be clinically feasible and could potentially be combined with immune stimulation to overcome the direct pro-metastatic effects of surgery, prevent immune suppression and enhance immunostimulatory responses. Accordingly, we believe that certain types of immunotherapy, together with interventions to abrogate stress-inflammatory responses, should be evaluated in conjunction with surgery and, for maximal effectiveness, could be initiated before administration of adjuvant therapies. Such strategies might improve the overall success of cancer treatment.
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Li Y, Dong W, Yang H, Xiao G. Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3. Biotechnol Lett 2020; 42:493-504. [PMID: 31894425 DOI: 10.1007/s10529-019-02787-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 12/20/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Propofol, an extensively used intravenous anesthetic agents during cancer resection surgery, has been confirmed to execute anti-tumor effect on multiple cancers, including colorectal cancer (CRC). Although the role of propofol in CRC has been previously reported, its action mechanism remains poorly understood. This study further explored the biological function and underlying mechanism of propofol in CRC cells. METHODS The cell proliferation, migration and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, wound healing assay and transwell assay, respectively. The expression levels microRNA-124-3p.1 (miR-124-3p.1) and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time polymerase chain reaction. Western blot assay was employed to measure the protein expression of MMP-9, Vimentin and Cyclin D1. The interaction between miR-124-3p.1 and AKT3 was predicted by TargetScan and confirmed by dual-luciferase reporter assay. RESULTS Propofol inhibited CRC cell proliferation, migration and invasion. Knockdown of miR-124-3p.1 or AKT3 upregulation reversed the inhibitory effects of propofol on CRC cell proliferation and metastasis. Besides, AKT3 was a direct target of miR-124-3p.1 and its overexpression abated the anti-tumor effect of miR-124-3p.1 on CRC cell proliferation and metastasis. CONCLUSION Propofol inhibited CRC cell proliferation, migration and invasion by upregulating miR-124-3p.1 and downregulating AKT3, providing a new sight for propofol treatment of CRC.
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Affiliation(s)
- Yujin Li
- Department of Anesthesiology, The First People's Hospital of Yunnan Province, Jin Bi Road, Xishan District, Kunming, 650000, Yunnan, China
| | - Wangjun Dong
- Department of Anesthesiology, Yongping County People's Hospital, Dali, 672600, Yunnan, China
| | - Hao Yang
- Department of Anesthesiology, The Second People's Hospital of Kunming, Kunming, 650000, Yunnan, China
| | - Gaopeng Xiao
- Department of Anesthesiology, The First People's Hospital of Yunnan Province, Jin Bi Road, Xishan District, Kunming, 650000, Yunnan, China.
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Ashrafizadeh M, Ahmadi Z, Farkhondeh T, Samarghandian S. Anti-tumor Activity of Propofol: A Focus on MicroRNAs. Curr Cancer Drug Targets 2020; 20:104-114. [PMID: 31657687 DOI: 10.2174/1568009619666191023100046] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 09/02/2019] [Accepted: 09/23/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND MicroRNAs are endogenous, short, non-coding RNAs with the length as low as 20 to 25 nucleotides. These RNAs are able to negatively affect the gene expression at the post-transcriptional level. It has been demonstrated that microRNAs play a significant role in cell proliferation, cell migration, cell death, cell differentiation, infection, immune response, and metabolism. Besides, the dysfunction of microRNAs has been observed in a variety of cancers. So, modulation of microRNAs is of interest in the treatment of disorders. OBJECTIVE The aim of the current review is to investigate the modulatory effect of propofol on microRNAs in cancer therapy. METHODS This review was performed at PubMed, SCOPUS and Web of Science data-bases using keywords "propofol', "microRNA", "cancer therapy", "propofol + microRNA" and "propofol + miR". RESULTS It was found that propofol dually down-regulates/upregulates microRNAs to exert its antitumor activity. In terms of oncogenesis microRNAs, propofol exert an inhibitory effect, while propofol significantly enhances the expression of oncosuppressor microRNAs. CONCLUSION It seems that propofol is a potential modulator of microRNAs and this capability can be used in the treatment of various cancers.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Zahra Ahmadi
- Department of Basic Science, Veterinary Medicine Faculty, Shushtar University, Khuzestan, Iran
| | - Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Saeed Samarghandian
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
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Effect of Equipotent Doses of Propofol versus Sevoflurane Anesthesia on Regulatory T Cells after Breast Cancer Surgery. Anesthesiology 2019; 129:921-931. [PMID: 30074934 DOI: 10.1097/aln.0000000000002382] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
WHAT WE ALREADY KNOW ABOUT THIS TOPIC WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery. METHODS A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated. RESULTS Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [-2.04 to 2.06], P = 0.995 for cluster of differentiation 39; -0.93 [-3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio. CONCLUSIONS Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery.
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Chen Z, Zhang P, Xu Y, Yan J, Liu Z, Lau WB, Lau B, Li Y, Zhao X, Wei Y, Zhou S. Surgical stress and cancer progression: the twisted tango. Mol Cancer 2019; 18:132. [PMID: 31477121 PMCID: PMC6717988 DOI: 10.1186/s12943-019-1058-3] [Citation(s) in RCA: 116] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 08/14/2019] [Indexed: 12/20/2022] Open
Abstract
Surgical resection is an important avenue for cancer treatment, which, in most cases, can effectively alleviate the patient symptoms. However, accumulating evidence has documented that surgical resection potentially enhances metastatic seeding of tumor cells. In this review, we revisit the literature on surgical stress, and outline the mechanisms by which surgical stress, including ischemia/reperfusion injury, activation of sympathetic nervous system, inflammation, systemically hypercoagulable state, immune suppression and effects of anesthetic agents, promotes tumor metastasis. We also propose preventive strategies or resolution of tumor metastasis caused by surgical stress.
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Affiliation(s)
- Zhiwei Chen
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Peidong Zhang
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Ya Xu
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China.,Deyang People's Hospital, Deyang, Sichuan, People's Republic of China
| | - Jiahui Yan
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Zixuan Liu
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Wayne Bond Lau
- Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, USA
| | - Bonnie Lau
- Department of Surgery, Emergency Medicine, Kaiser Santa Clara Medical Center, Affiliate of Stanford University, Stanford, USA
| | - Ying Li
- Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, People's Republic of China
| | - Xia Zhao
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Yuquan Wei
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Shengtao Zhou
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China.
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Argano M, De Maria R, Rodlsberger K, Buracco P, Menzies MPL. Use of a colorimetric assay to evaluate the proliferation of canine mammary tumor cells exposed to propofol. CANADIAN JOURNAL OF VETERINARY RESEARCH = REVUE CANADIENNE DE RECHERCHE VETERINAIRE 2019; 83:149-153. [PMID: 31097877 PMCID: PMC6450161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 10/07/2018] [Indexed: 06/09/2023]
Abstract
Drugs applied on human cancer cells can influence the rate of cell proliferation. The present study investigates the use of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) colorimetric assay to evaluate canine tumor cell proliferation after exposure to the injectable anesthetic, propofol. Primary (CIPp) and metastatic (CIPm) canine tubular adenocarcinoma cell lines were incubated with cell culture medium (control) or propofol (1, 5, and 10 μg/mL). The MTT assays were performed after 6 and 12 hours of exposure. Measurements of absorbance were obtained for each condition with a spectrophotometer and compared with controls using a 3-way analysis of variance (P < 0.05). An increased cell proliferation rate was observed in CIPp exposed to 5 and 10 μg/mL of propofol for 6 hours and 1, 5, and 10 μg/mL for 12 hours. No significant changes were observed in CIPm after 6 hours of exposure. All propofol concentrations decreased the cell proliferation rate in CIPm after 12 hours of exposure. The MTT assays showed that exposure of CIPp to propofol for 6 and 12 hours increased cell proliferation. A decrease in the CIPm proliferation rate was observed when propofol exposure lasted for 12 hours. Further studies are warranted to better understand the role of propofol on cancer cell proliferation.
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Affiliation(s)
- Martina Argano
- Anaesthesiology and Perioperative Intensive-Care Medicine, Veterinary University Vienna, Veterinaerplatz 1, 1210 Vienna, Austria (Argano, Rodlsberger, Menzies); Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland (Argano); Department of Veterinary Sciences-Surgery Unit, Veterinary Faculty of the University of Turin, Italy (De Maria, Buracco)
| | - Raffaella De Maria
- Anaesthesiology and Perioperative Intensive-Care Medicine, Veterinary University Vienna, Veterinaerplatz 1, 1210 Vienna, Austria (Argano, Rodlsberger, Menzies); Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland (Argano); Department of Veterinary Sciences-Surgery Unit, Veterinary Faculty of the University of Turin, Italy (De Maria, Buracco)
| | - Katrin Rodlsberger
- Anaesthesiology and Perioperative Intensive-Care Medicine, Veterinary University Vienna, Veterinaerplatz 1, 1210 Vienna, Austria (Argano, Rodlsberger, Menzies); Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland (Argano); Department of Veterinary Sciences-Surgery Unit, Veterinary Faculty of the University of Turin, Italy (De Maria, Buracco)
| | - Paolo Buracco
- Anaesthesiology and Perioperative Intensive-Care Medicine, Veterinary University Vienna, Veterinaerplatz 1, 1210 Vienna, Austria (Argano, Rodlsberger, Menzies); Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland (Argano); Department of Veterinary Sciences-Surgery Unit, Veterinary Faculty of the University of Turin, Italy (De Maria, Buracco)
| | - M Paula Larenza Menzies
- Anaesthesiology and Perioperative Intensive-Care Medicine, Veterinary University Vienna, Veterinaerplatz 1, 1210 Vienna, Austria (Argano, Rodlsberger, Menzies); Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland (Argano); Department of Veterinary Sciences-Surgery Unit, Veterinary Faculty of the University of Turin, Italy (De Maria, Buracco)
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Chu X, Zhou Q, Xu Y, Jiang J, Li Q, Zhou Q, Wu Q, Jin M, Wang H, Gu Y, Wang X, Wang B, He S, He X, Wu C, Zhang F, Zhang Y. Aberrant fatty acid profile and FFAR4 signaling confer endocrine resistance in breast cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2019; 38:100. [PMID: 30795784 PMCID: PMC6387561 DOI: 10.1186/s13046-019-1040-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 01/15/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND Evidence suggests that fatty acid receptor FFAR4 plays a tumor-promoting role in adipose tissue-adjacent malignancies, but its clinical relevance remains unexplored. Here, we investigated the clinical significance and underlying mechanisms of FFAR4 in hormone receptor-positive breast cancer (HRPBC). METHODS FFAR4 expression was assessed by immunohistochemistry in an exploration cohort of 307 breast cancer cases collected from two independent institutes. Two public breast cancer microarray datasets served as validation cohorts. Gas chromatography-mass spectrometry was employed to identify FFAR4 ligands in normal and cancerous breast tissues. Survival analyses were performed in all cohorts and designated molecular subgroups. Mechanistic studies were performed in vitro in hormone receptor-positive breast cancer cell lines MCF-7 and T-47D. RESULTS Aberrant FFAR4 expression and endogenous FFAR4 ligands were identified in breast cancer tissues, five FFAR4 ligands showed significantly elevated proportions in cancerous versus normal tissues. In the exploration cohort, FFAR4 was demonstrated as an independent prognostic factor for recurrences (HR: 2.183, 95% CI: 1.360-3.504, P = 0.001) and breast cancer-specific deaths (HR: 2.102, 95% CI: 1.173-3.766, P = 0.013) in HRPBC cases. In contrast, FFAR4 expression was not associated with prognosis in hormone receptor-negative cases. In the validation cohorts, FFAR4 mRNA levels were also observed to be associated with disease recurrence in estrogen receptor-positive cases, but not so in estrogen receptor-negative cases. FFAR4 activation by endogenous ligands and a synthetic ligand TUG891 significantly dampened tamoxifen's efficacy on HRPBC cells, whereas FFAR4 knockdown or antagonist AH7614 abrogated this effect. Furthermore, FFAR4-induced tamoxifen resistance was dependent on ERK and AKT pathways in HRPBC. CONCLUSIONS Our results establish a novel role of FFAR4 and its ligands in the complicated interactions between tissue lipid profile and cancer biology. FFAR4 signaling confers tamoxifen resistance in HRPBC cell line and FFAR4 expression can serve as a prognostic biomarker for tamoxifen-treated HRPBC patients. FFAR4 may serve as a potential target for anti-breast cancer therapies, especially in endocrine resistant cases.
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Affiliation(s)
- Xiao Chu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China.,Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.,Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Qi Zhou
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China
| | - Yingchun Xu
- Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
| | - Jingting Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China
| | - Qing Li
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China
| | - Qianjun Zhou
- Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Qiong Wu
- Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Min Jin
- Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Hui Wang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China
| | - Yuting Gu
- Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
| | - Xue Wang
- Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Bei Wang
- Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Songbing He
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China
| | - Xiaozhou He
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China
| | - Changping Wu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China.
| | - Fengchun Zhang
- Department of Oncology, Suzhou Kowloon Hospital and Shanghai Ruijin Hospital, SJTUSM, Suzhou, Jiangsu, China.
| | - Yanyun Zhang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Changzhou, Jiangsu, China. .,Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
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Niga P, Hansson-Mille PM, Swerin A, Claesson PM, Schoelkopf J, Gane PAC, Dai J, Furó I, Campbell RA, Johnson CM. Propofol adsorption at the air/water interface: a combined vibrational sum frequency spectroscopy, nuclear magnetic resonance and neutron reflectometry study. SOFT MATTER 2018; 15:38-46. [PMID: 30516226 DOI: 10.1039/c8sm01677a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Propofol is an amphiphilic small molecule that strongly influences the function of cell membranes, yet data regarding interfacial properties of propofol remain scarce. Here we consider propofol adsorption at the air/water interface as elucidated by means of vibrational sum frequency spectroscopy (VSFS), neutron reflectometry (NR), and surface tensiometry. VSFS data show that propofol adsorbed at the air/water interface interacts with water strongly in terms of hydrogen bonding and weakly in the proximity of the hydrocarbon parts of the molecule. In the concentration range studied there is almost no change in the orientation adopted at the interface. Data from NR show that propofol forms a dense monolayer with a thickness of 8.4 Å and a limiting area per molecule of 40 Å2, close to the value extracted from surface tensiometry. The possibility that islands or multilayers of propofol form at the air/water interface is therefore excluded as long as the solubility limit is not exceeded. Additionally, measurements of the 1H NMR chemical shifts demonstrate that propofol does not form dimers or multimers in bulk water up to the solubility limit.
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Affiliation(s)
- Petru Niga
- RISE Research Institutes of Sweden - Chemistry, Materials and Surfaces, Box 5607, SE-114 86 Stockholm, Sweden.
| | - Petra M Hansson-Mille
- RISE Research Institutes of Sweden - Chemistry, Materials and Surfaces, Box 5607, SE-114 86 Stockholm, Sweden.
| | - Agne Swerin
- RISE Research Institutes of Sweden - Chemistry, Materials and Surfaces, Box 5607, SE-114 86 Stockholm, Sweden. and KTH Royal Institute of Technology, Department of Chemistry, Division of Surface and Corrosion Science, SE-100 44 Stockholm, Sweden.
| | - Per M Claesson
- RISE Research Institutes of Sweden - Chemistry, Materials and Surfaces, Box 5607, SE-114 86 Stockholm, Sweden. and KTH Royal Institute of Technology, Department of Chemistry, Division of Surface and Corrosion Science, SE-100 44 Stockholm, Sweden.
| | | | - Patrick A C Gane
- Omya International AG, Baslerstrasse 42, CH-4665 Oftringen, Switzerland and Aalto University, School of Chemical Technology, Department of Bioproducts and Biosystems, FI-00076 Aalto, Helsinki, Finland
| | - Jing Dai
- KTH Royal Institute of Technology, Department of Chemistry, Division of Applied Physical Chemistry, SE-100 44 Stockholm, Sweden
| | - István Furó
- KTH Royal Institute of Technology, Department of Chemistry, Division of Applied Physical Chemistry, SE-100 44 Stockholm, Sweden
| | - Richard A Campbell
- Institut Laue-Langevin, 71 Avenue des Martyrs, CS20156, 38042 Grenoble Cedex 9, France and Division of Pharmacy and Optometry, University of Manchester, Manchester M13 9PT, UK
| | - C Magnus Johnson
- KTH Royal Institute of Technology, Department of Chemistry, Division of Surface and Corrosion Science, SE-100 44 Stockholm, Sweden.
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Propofol inhibits proliferation, migration and invasion of gastric cancer cells by up-regulating microRNA-195. Int J Biol Macromol 2018; 120:975-984. [DOI: 10.1016/j.ijbiomac.2018.08.173] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 08/28/2018] [Accepted: 08/28/2018] [Indexed: 12/22/2022]
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Zhang Z, Zang M, Wang S, Wang C. Effects of propofol on human cholangiocarcinoma and the associated mechanisms. Exp Ther Med 2018; 17:472-478. [PMID: 30651824 DOI: 10.3892/etm.2018.6908] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 07/26/2018] [Indexed: 12/17/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the most common type of biliary duct malignancy. Propofol is a fast-acting intravenous anesthetic, which also exerts an anti-cancer effect. The aim of the current study was to explore the effects of propofol on human CCA and the associated mechanisms in vitro. The results indicated that as concentration (0, 1, 5 and 10 µg/ml) of propofol and treatment time (24, 48 and 72 h) increased, the cell inhibition rate of human CCA QBC939 cells increased. Furthermore, treatment with various concentrations of propofol for 48 h resulted in a decrease in migration and invasion capacity in QBC939 cells. Propofol also induced the apoptosis of QBC939 cells and cell cycle arrest in G1 phase. Propofol treatment increased the expression level of Bax and decreased that of Bcl-2. In addition, the effects of propofol on gene expression were evaluated, including Wnt3α, β-catenin, Snail1 and c-myc in the Wnt/β-catenin signaling pathway. It was identified that as the concentration of propofol increased, the expression of these genes decreased. In conclusion, the current results indicate that propofol is a promising therapeutic agent for the treatment of CCA.
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Affiliation(s)
- Zhuo Zhang
- Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Mingcui Zang
- Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Shuang Wang
- Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Chunli Wang
- Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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Li R, Liu H, Dilger JP, Lin J. Effect of Propofol on breast Cancer cell, the immune system, and patient outcome. BMC Anesthesiol 2018; 18:77. [PMID: 29945542 PMCID: PMC6020422 DOI: 10.1186/s12871-018-0543-3] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 06/11/2018] [Indexed: 12/14/2022] Open
Abstract
Breast cancer is the second leading cause of cancer death in women. Surgery is the first line of treatment for breast cancer. Retrospective clinical studies suggest that the type of anesthesia administered during oncological surgery may influence patient outcome. Propofol, the widely used intravenous anesthetic agent, may lead to better outcomes compared to volatile anesthetics. Here we review the literature on the effect of propofol in breast cancer cells, the immune system, pain management, and patient outcomes. Evidence from the study of breast cancer cell lines suggests that high concentrations of propofol have both anti-tumor and pro-tumor effects. Propofol and volatile anesthetics have different effects on the immune system. Propofol has also been shown to reduce the development and severity of acute and chronic pain following surgery. Although a retrospective study that included many types of cancer indicated that propofol increases the long-term survival of patients following surgery, the evidence for this in breast cancer is weak. It has been shown that Propofol combined with paravertebral block led to change of serum composition that affects the breast cancer cell behaviors and natural killer cell activity. Prospective studies are in progress and will be finished within 5 years. The existing evidence is not sufficient to warrant changes to current anesthetic management. Further research is needed to clarify the mechanisms by which propofol affects cancer cells and the immune system.
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Affiliation(s)
- Ru Li
- Department of Anesthesiology, Stony Brook University Health Sciences Center, Stony Brook, NY, 11794-8480, USA
| | - Hengrui Liu
- Department of Anesthesiology, Stony Brook University Health Sciences Center, Stony Brook, NY, 11794-8480, USA
| | - James P Dilger
- Department of Anesthesiology, Stony Brook University Health Sciences Center, Stony Brook, NY, 11794-8480, USA
| | - Jun Lin
- Department of Anesthesiology, Stony Brook University Health Sciences Center, Stony Brook, NY, 11794-8480, USA.
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Chen X, Li K, Zhao G. Propofol Inhibits HeLa Cells by Impairing Autophagic Flux via AMP-Activated Protein Kinase (AMPK) Activation and Endoplasmic Reticulum Stress Regulated by Calcium. Med Sci Monit 2018; 24:2339-2349. [PMID: 29667627 PMCID: PMC5926273 DOI: 10.12659/msm.909144] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Background Propofol has antitumor effects against various cancers. However, the mechanism of action of propofol in HeLa human cervical cancer cells has not been elucidated. Material/Methods We treated HeLa human cervical cancer cells with different concentrations of propofol. Cell viability was evaluated with Cell Counting Kit-8 and apoptosis was analyzed by annexin V-fluorescein isothiocyanate and propidium iodide staining and flow cytometry. Autophagosome formation was evaluated based on microtubule-associated protein light chain (LC)3 conversion and light chain 3 puncta formation. Autophagosome clearance was assessed according to p62 protein level and autolysosome generation. Results We found that propofol decreased cell viability and increased autophagosome generation in HeLa cells. Autophagosome formation was evaluated based on LC3 conversion and LC3 puncta formation. Autophagosome clearance was assessed according to p62 protein level. The AMPK/mTOR signaling pathway was found to be activated in propofol-induced autophagosome accumulation. Fluorescence analysis using LysoTracker dye revealed that propofol blocked autophagosome–lysosome fusion. Administration of rapamycin increased autophagosome clearance in propofol-treated HeLa cells. Additionally, propofol induced endoplasmic reticulum (ER) stress and disrupted intracellular Ca2+ balance, thereby enhancing autophagosome accumulation. Suppressing ER stress by treatment with tauroursodeoxycholic acid (TUDCA) enhanced these effects, suggesting that the cytotoxicity of propofol is related to induction of ER stress. Conclusions This study is the first to provide evidence that propofol-mediated autophagy regulation is an underlying part of the mechanism by which propofol regulates HeLa cells progression.
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Affiliation(s)
- Xi Chen
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China (mainland)
| | - Kai Li
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China (mainland)
| | - Guoqing Zhao
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China (mainland)
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Wang H, Zhang S, Zhang A, Yan C. Propofol Prevents the Progression of Malignant PheochromocytomaIn VitroandIn Vivo. DNA Cell Biol 2018; 37:308-315. [PMID: 29565198 DOI: 10.1089/dna.2017.3972] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Hua Wang
- Department of Endocrinology, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin, China
| | - Shu Zhang
- Department of Endocrinology, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin, China
| | - Aihong Zhang
- Department of Pharmaceuticals, Harbin Medical University Affiliated 3rd Hospital, Harbin, China
| | - Cunling Yan
- Department of Medicine, Harbin Medical University Affiliated 3rd Hospital, Harbin, China
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Hsu SS, Jan CR, Liang WZ. Evaluation of cytotoxicity of propofol and its related mechanism in glioblastoma cells and astrocytes. ENVIRONMENTAL TOXICOLOGY 2017; 32:2440-2454. [PMID: 28804952 DOI: 10.1002/tox.22458] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 07/25/2017] [Accepted: 07/27/2017] [Indexed: 06/07/2023]
Abstract
Propofol (2,6-diisopropylphenol), one of the extensively and commonly used anesthetic agents, has been shown to affect the biological behavior of various models. Previous researches have shown that propofol-induced cytotoxicity might cause anticancer effect in different cells. However, the mechanisms underlying the effect of propofol on cytotoxicity is still elusive in human glioblastoma cells. The aims of this study were to evaluate effects of propofol on cytotoxicity, cell cycle distribution and ROS production, and establish the relationship between oxidative stress and cytotoxicity in GBM 8401 human glioblastoma cells and DI TNC1 rat astrocytes. Propofol (20-30 μM) concentration-dependently induced cytotoxicity, cell cycle arrest, and increased ROS production in GBM 8401 cells but not in DI TNC1 cells. In GBM 8401 cells, propofol induced G2/M phase cell arrest, which affected the CDK1, cyclin B1, p53, and p21 protein expression levels. Furthermore, propofol induced oxygen stresses by increasing O2- and H2 O2 levels but treatment with the antioxidant N-acetylcysteine (NAC) partially reversed propofol-regulated antioxidative enzyme levels (superoxide dismutase, catalase, and glutathione peroxidase). Most significantly, propofol induced apoptotic effects by decreasing Bcl-2 but increasing Bax, cleaved caspase-9/caspase-3 levels, which were partially reversed by NAC. Moreover, the pancaspase inhibitor Z-VAD-FMK also partially prevented propofol-induced apoptosis. Together, in GBM 8401 cells but not in DI TNC1 cells, propofol activated ROS-associated apoptosis that involved cell cycle arrest and caspase activation. These findings indicate that propofol not only can be an anesthetic agent which reduces pain but also has the potential to be used for the treatment of human glioblastoma.
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Affiliation(s)
- Shu-Shong Hsu
- Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 813, Republic of China
- Department of Surgery, National Defense Medical Center, Taipei, Taiwan, 114, Republic of China
| | - Chung-Ren Jan
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 813, Republic of China
| | - Wei-Zhe Liang
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 813, Republic of China
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Tan Z, Peng A, Xu J, Ouyang M. Propofol enhances BCR-ABL TKIs' inhibitory effects in chronic myeloid leukemia through Akt/mTOR suppression. BMC Anesthesiol 2017; 17:132. [PMID: 28962554 PMCID: PMC5622516 DOI: 10.1186/s12871-017-0423-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 09/19/2017] [Indexed: 12/26/2022] Open
Abstract
Background The anti-cancer activities of intravenous anesthetic drug propofol have been demonstrated in various types of cancers but not in chronic myeloid leukemia (CML). Methods We systematically examined the effect of propofol and its combination with BCR-ABL tyrosine kinase inhibitors (TKIs) in CML cell lines, patient progenitor cells and mouse xenograft model. We analyzed propofol’s underlying mechanism focusing on survival pathway in CML cells. Results We show that propofol alone is active in inhibiting proliferation and inducing apoptosis in KBM-7, KU812 and K562 cells, and acts synergistically with imatinib or dasatinib, in in vitro cell culture system and in vivo xenograft model. In addition, propofol is more effective in inducing apoptosis and inhibiting colony formation in CML CD34 progenitor cells than normal bone marrow (NBM) counterparts. Combination of propofol and dasatinib significantly eliminates CML CD34 without affecting NBM CD34 cells. We further demonstrate that propofol suppresses phosphorylation of Akt, mTOR, S6 and 4EBP1 in K562. Overexpression of constitutively active Akt significantly reverses the inhibitory effects of propofol in K562, confirm that propofol acts on CML cells via inhibition of Akt/mTOR. Interestingly, the levels of p-Akt, p-mTOR and p-S6 are lower in cells treated with combination of propofol and imatinib than cells treated with propofol or imatinib alone, suggesting that propofol augments BCR-ABL TKI’s inhibitory effect via suppressing Akt/mTOR pathway. Conclusion Our work shows that propofol can be repurposed to for CML treatment. Our findings highlight the therapeutic value of Akt/mTOR in overcoming resistance to BCR-ABL TKI treatment in CML. Electronic supplementary material The online version of this article (10.1186/s12871-017-0423-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Zhimin Tan
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Xinhu Road No.1333, Bao'an district, Shenzhen, 518100, Guangdong province, China
| | - Aixia Peng
- Department of Oncology, Shenzhen Hospital, Southern Medical University, Xinhu Road No.1333, Bao'an district, Shenzhen, 518100, Guangdong province, China
| | - Jingwen Xu
- Department of Anesthesiology, Fifth Affiliated Hospital, Southern Medical University, Congcheng Road No. 566, Conghua district, Guangzhou, Guangdong province, 510900, China
| | - Mingwen Ouyang
- Department of Anesthesiology, Fifth Affiliated Hospital, Southern Medical University, Congcheng Road No. 566, Conghua district, Guangzhou, Guangdong province, 510900, China.
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Tatsumi K, Hirotsu A, Daijo H, Matsuyama T, Terada N, Tanaka T. Effect of propofol on androgen receptor activity in prostate cancer cells. Eur J Pharmacol 2017; 809:242-252. [PMID: 28552345 DOI: 10.1016/j.ejphar.2017.05.046] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 05/15/2017] [Accepted: 05/24/2017] [Indexed: 01/10/2023]
Abstract
Androgen receptor is a nuclear receptor and transcription factor activated by androgenic hormones. Androgen receptor activity plays a pivotal role in the development and progression of prostate cancer. Although accumulating evidence suggests that general anesthetics, including opioids, affect cancer cell growth and impact patient prognosis, the effect of those drugs on androgen receptor in prostate cancer is not clear. The purpose of this study was to investigate the effect of the general anesthetic propofol on androgen receptor activity in prostate cancer cells. An androgen-dependent human prostate cancer cell line (LNCaP) was stimulated with dihydrotestosterone (DHT) and exposed to propofol. The induction of androgen receptor target genes was investigated using real-time reverse transcription polymerase chain reaction, and androgen receptor protein levels and localization patterns were analyzed using immunoblotting and immunofluorescence assays. The effect of propofol on the proliferation of LNCaP cells was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Propofol significantly inhibited DHT-induced expression of androgen receptor target genes in a dose- and time-dependent manner, and immunoblotting and immunofluorescence assays indicated that propofol suppressed nuclear levels of androgen receptor proteins. Exposure to propofol for 24h suppressed the proliferation of LNCaP cells, whereas 4h of exposure did not exert significant effects. Together, our results indicate that propofol suppresses nuclear androgen receptor protein levels, and inhibits androgen receptor transcriptional activity and proliferation in LNCaP cells.
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Affiliation(s)
- Kenichiro Tatsumi
- Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
| | - Akiko Hirotsu
- Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
| | - Hiroki Daijo
- Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
| | - Tomonori Matsuyama
- Department of Anesthesia, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-0861, Japan
| | - Naoki Terada
- Department of Urology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
| | - Tomoharu Tanaka
- Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
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Dumas F, Haanappel E. Lipids in infectious diseases - The case of AIDS and tuberculosis. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2017; 1859:1636-1647. [PMID: 28535936 DOI: 10.1016/j.bbamem.2017.05.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 05/11/2017] [Accepted: 05/14/2017] [Indexed: 02/07/2023]
Abstract
Lipids play a central role in many infectious diseases. AIDS (Acquired Immune Deficiency Syndrome) and tuberculosis are two of the deadliest infectious diseases to have struck mankind. The pathogens responsible for these diseases, Human Immunodeficiency Virus-1 and Mycobacterium tuberculosis, rely on lipids and on lipid membrane properties to gain access to their host cells, to persist in them and ultimately to egress from their hosts. In this Review, we discuss the life cycles of these pathogens and the roles played by lipids and membranes. We then give an overview of therapies that target lipid metabolism, modulate host membrane properties or implement lipid-based drug delivery systems. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
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Affiliation(s)
- Fabrice Dumas
- Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France.
| | - Evert Haanappel
- Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France
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Meng C, Song L, Wang J, Li D, Liu Y, Cui X. Propofol induces proliferation partially via downregulation of p53 protein and promotes migration via activation of the Nrf2 pathway in human breast cancer cell line MDA-MB-231. Oncol Rep 2016; 37:841-848. [PMID: 28035403 DOI: 10.3892/or.2016.5332] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 07/14/2016] [Indexed: 11/06/2022] Open
Abstract
Antioxidants induce the proliferation of cancers by decreasing the expression of p53. Propofol, one of the most extensively used intravenous anesthetics, provides its antioxidative activity via activation of the nuclear factor E2-related factor-2 (Nrf2) pathway, but the mechanisms involved in the effects remain unknown. Thus, we aimed to investigate the function of p53 and Nrf2 in the human breast cancer cell line MDA-MB-231 following treatment with propofol. The cells were treated with propofol (2, 5 and 10 µg/ml) for 1, 4 and 12 h, and MTT assay was used to evaluate cell proliferation, and a wound healing assay was used to evaluate cell migration. Cell apoptosis, caspase-3 activity, and western blot analysis for p53 and Nrf2 protein were also assessed. Finally, PIK-75, a potent Nrf2 inhibitor, was used to confirm the effects of Nrf2 after treatment with propofol. Treatment of MDA-MB‑231 cells with propofol resulted in increased proliferation and migration in a dose- and time-dependent manner. After treatment with propofol for 12 h, the Nrf2 protein expression was increased, while the percentage of apoptotic cells, caspase-3 activity, and expression of p53 were significantly decreased. Additionally, treatment with the Nrf2 inhibitor increased the percentage of apoptotic cells, inhibited the migration almost completely, and decreased the degree of proliferation, while the expression of p53 was not affected. In conclusion, propofol increased the proliferation of human breast cancer MDA-MB‑231 cells, which was at least partially associated with the inhibition of the expression of p53, and induced cell migration, which was involved in the activation of the Nrf2 pathway.
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Affiliation(s)
- Chao Meng
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, and Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Harbin, Heilongjiang 150001, P.R. China
| | - Linlin Song
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, and Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Harbin, Heilongjiang 150001, P.R. China
| | - Juan Wang
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, and Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Harbin, Heilongjiang 150001, P.R. China
| | - Di Li
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, and Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Harbin, Heilongjiang 150001, P.R. China
| | - Yanhong Liu
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, and Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Harbin, Heilongjiang 150001, P.R. China
| | - Xiaoguang Cui
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, and Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Harbin, Heilongjiang 150001, P.R. China
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Cell membrane modulation as adjuvant in cancer therapy. Cancer Treat Rev 2016; 52:48-57. [PMID: 27889637 DOI: 10.1016/j.ctrv.2016.10.008] [Citation(s) in RCA: 257] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 10/24/2016] [Accepted: 10/27/2016] [Indexed: 12/25/2022]
Abstract
Cancer is a complex disease involving numerous biological processes, which can exist in parallel, can be complementary, or are engaged when needed and as such can replace each other. This redundancy in possibilities cancer cells have, are fundamental to failure of therapy. However, intrinsic features of tumor cells and tumors as a whole provide also opportunities for therapy. Here we discuss the unique and specific makeup and arrangement of cell membranes of tumor cells and how these may help treatment. Interestingly, knowledge on cell membranes and associated structures is present already for decades, while application of membrane modification and manipulation as part of cancer therapy is lagging. Recent developments of scientific tools concerning lipids and lipid metabolism, opened new and previously unknown aspects of tumor cells and indicate possible differences in lipid composition and membrane function of tumor cells compared to healthy cells. This field, coined Lipidomics, demonstrates the importance of lipid components in cell membrane in several illnesses. Important alterations in cancer, and specially in resistant cancer cells compared to normal cells, opened the door to new therapeutic strategies. Moreover, the ability to modulate membrane components and/or properties has become a reality. Here, developments in cancer-related Lipidomics and strategies to interfere specifically with cancer cell membranes and how these affect cancer treatment are discussed. We hypothesize that combination of lipid or membrane targeted strategies with available care to improve chemotherapy, radiotherapy and immunotherapy will bring the much needed change in treatment in the years to come.
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Biophysics in cancer: The relevance of drug-membrane interaction studies. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2016; 1858:2231-2244. [DOI: 10.1016/j.bbamem.2016.06.025] [Citation(s) in RCA: 116] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 05/31/2016] [Accepted: 06/26/2016] [Indexed: 12/26/2022]
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Abstract
Considerable debate exists regarding the potential antineoplastic effect of dietary long-chain n-3 PUFA contained in fatty fishes. Since the majority of published data has proven that their intake does not induce toxic or carcinogenic effects in humans, their possible preventive use against cancer has been suggested. On the other hand, it is unlikely that they could be effective in cancer patients as a single therapy. Nevertheless, a considerable effort has been put forth in recent years to evaluate the hypothesis that n-3 PUFA might improve the antineoplastic efficiency of currently used anticancer agents. The rationale for this therapeutic combinatory strategy is trying to increase cancer sensitivity to conventional therapies. This could allow the use of lower drug/radiation doses and, thereby, a reduction in the detrimental health effects associated with these treatments. We will here critically examine the studies that have investigated this possibility, by focusing particularly on the biological and molecular mechanisms underlying the antineoplastic effect of these combined treatments. A possible use of n-3 PUFA in combination with the innovative single-targeted anti-cancer therapies, that often are not completely devoid of dangerous side-effects, is also suggested.
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Khan AA, Alanazi AM, Jabeen M, Hassan I, Bhat MA. Targeted nano-delivery of novel omega-3 conjugate against hepatocellular carcinoma: Regulating COX-2/bcl-2 expression in an animal model. Biomed Pharmacother 2016; 81:394-401. [PMID: 27261618 DOI: 10.1016/j.biopha.2016.04.033] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2015] [Revised: 04/14/2016] [Accepted: 04/17/2016] [Indexed: 12/30/2022] Open
Abstract
The present approach enumerates the effectiveness of tuftsin tagged nano-liposome for the cytosolic transport of 2,6-di-isopropylphenol-linolenic acid conjugate against liver cancer in mice. Initially, the conjugate in its free form was examined for anticancer potential on HepG2 liver cancer cells. Induction of apoptosis and suppression of migration and adhesion of HepG2 cells confirmed the effectiveness of conjugate as an anticancer agent. After this, role of the conjugate entrapped in a nano-carrier was evaluated in animal model. The nano-formulation comprising of conjugate bearing tuftsin tagged liposome was firsly characterized and then its therapeutic effect was determined. The nano-formulation had 100-130nm size nanoparticles and showed sustained release of the conjugate in the surrounding milieu. The nano-formulation distinctly reduced the expression of COX-2, an important molecule that is vastly expressed in hepatocellular carcinoma. The utilization of in-house engineered nano-formulation was also successful in significantly up-regulating Bax and down-regulating bcl-2 gene expression eventually helping in better survival of treated mice. Histopathological analysis also revealed positive recovery of the general architecture and the violent death of cancer cells by apoptosis at tumor specific site. The site specific delivery of conjugate entrapped in tuftsin tagged liposomes was highly safe as well as efficaceous. Nano-formulation based approach showed a visible chemotherapeutic effect on liver cancer progression in experimental mice thereby making it a potential candidate for treatment of liver cancer in clinical settings.
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Affiliation(s)
- Azmat Ali Khan
- Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Amer M Alanazi
- Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mumtaz Jabeen
- Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Iftekhar Hassan
- Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mashooq Ahmad Bhat
- Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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Yasa SR, Kaki SS, Rao BB, Jain N, Penumarthy V. Synthesis, characterization and evaluation of antiproliferative activity of diisopropylphenyl esters of fatty acids from selected oils. Med Chem Res 2016. [DOI: 10.1007/s00044-016-1564-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Reddy YS, Kaki SS, Rao BB, Jain N, Vijayalakshmi P. Study on Synthesis, Characterization and Antiproliferative Activity of Novel Diisopropylphenyl Esters of Selected Fatty Acids. J Oleo Sci 2016; 65:81-9. [DOI: 10.5650/jos.ess15151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Yasa Sathyam Reddy
- Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology (CSIR-IICT)
| | - Shiva Shanker Kaki
- Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology (CSIR-IICT)
| | - Bala Bhaskara Rao
- Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT)
| | - Nishant Jain
- Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT)
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Lee BM, Cata JP. Impact of anesthesia on cancer recurrence. REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION 2015; 62:570-575. [PMID: 26026503 DOI: 10.1016/j.redar.2015.04.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 03/31/2015] [Accepted: 04/02/2015] [Indexed: 06/04/2023]
Abstract
Surgery remains the mainstay treatment in the majority of solid cancers. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system, inflammation and angiogenesis, and have a direct effect on cancer cells that could ultimately modify oncological outcomes. For instance, volatile anesthetics and opioid analgesics have shown predominantly pro-tumor effects, while propofol, non-steroid anti-inflammatory drugs have mostly anticancer effects. Researchers have been especially interested in investigating the association between the use of regional anesthesia techniques and the postoperative survival of patients with cancers. Since the results of the current retrospective studies are conflicting, several researchers are conducting prospective randomized trials.
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Affiliation(s)
- B M Lee
- Department of Anaesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Cancer, Houston, TX, USA
| | - J P Cata
- Department of Anaesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Cancer, Houston, TX, USA; Anesthesia and Surgical Oncological Research Group, TX, USA.
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Propofol promotes cell apoptosis via inhibiting HOTAIR mediated mTOR pathway in cervical cancer. Biochem Biophys Res Commun 2015; 468:561-7. [PMID: 26523512 DOI: 10.1016/j.bbrc.2015.10.129] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 10/24/2015] [Indexed: 12/26/2022]
Abstract
OBJECTIVES Cervical cancer is one of the most common gynecologic malignant tumors. Propofol has been proposed to play a role of antitumor in various cancers. However, the functions and mechanisms of Propofol in cervical cancer is still not clear. METHODS In vitro, the different concentrations of propofol were co-incubated with cervical cancer cell lines, including Hela, Caski and C-33A cells respectively. The pcDNA-HOTAIR plasmid was transfected into cells after the treatment of 10 μg/ml propofol. The cell viability and apoptosis were detected by MTT assay and TUNEL method. In vivo, propofol was injected into mice of transplantation tumor with Caski cells or with pcDNA-HOTAIR treated Caski cells. RESULTS Propofol significantly decreased the cell viability and increased the cell apoptosis in Hela, Caski and C-33A cells, while HOTAIR overexpression promoted cell viability and inhibits cell apoptosis. mTOR/p70S6K protein expression levels were also markedly reduced by propofol but the effects were reversed with pcDNA-HOTAIR. In vivo, propofol inhibited the tumor size but had no inhibition effect in HOTAIR overexpression group. CONCLUSION Propofol inhibited tumor size, cell viability and promoted cell apoptosis via inhibiting mTOR/p70S6K pathway mediated by HOTAIR in cervical cancer.
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Abstract
Polyphenols and n-3 polyunsaturated fatty acids (PUFAs) are two classes of natural compounds, which have been highlighted in epidemiological studies for their health benefits. The biological activities of those two families of metabolites on oxidation, inflammation, cancer, cardiovascular and degenerative diseases have been reported in vitro and in vivo. On the other hand, chemical bonding between the two structures leading to n-3 lipophenol derivatives (or phenolipids) has been studied in numerous works over the last decade, and some examples could also be found from natural sources. Interest in lipophilization of phenolic structures is various and depends on the domain of interest: in food industry, the development of lipidic antioxidants could be performed to protect lipidic food matrix from oxidation. Whereas, on pharmaceutical purpose, increasing the lipophilicity of polar phenolic drugs could be performed to improve their pharmacological profile. Moreover, combining both therapeutic aspects of n-3 PUFAs and of polyphenols in a single lipophenolic molecule could also be envisaged. An overview of the synthesis and of the natural sources of n-3 lipophenols is presented here, in addition to their biological activities which point out in several cases the benefit of the conjugated derivatives.
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Xu J, Xu W, Zhu J. Propofol suppresses proliferation and invasion of glioma cells by upregulating microRNA-218 expression. Mol Med Rep 2015; 12:4815-20. [PMID: 26133092 PMCID: PMC4581763 DOI: 10.3892/mmr.2015.4014] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Accepted: 11/19/2014] [Indexed: 01/06/2023] Open
Abstract
Propofol (2,6-diisopropylphenol) is a commonly used intravenous anesthetic agent. The present study aimed to assess the effect of propofol on the proliferation and invasion of human glioma cells, and to determine the potential underlying molecular mechanisms. The effects of propofol on U373 glioblastoma cell proliferation, apoptosis and invasion were detected by an MTT assay, caspase‑3 activity measurement and a Matrigel™ invasion assay, respectively. MicroRNA (miR)‑218 expression and matrix metalloproteinase (MMP)‑2 protein expression levels were analyzed by quantitative polymerase chain reaction and western blot analysis, respectively. In addition, miR‑218 precursor was transfected into the cells to assess whether overexpression of miR‑218 could affect MMP‑2 expression. Anti‑miR‑218 was transfected into the cells to evaluate the role of miR‑218 in the effects of propofol on the biological behavior of glioma cells. The results of the present study demonstrated that propofol significantly increased the expression levels of miR‑218, inhibited U373 cell proliferation and invasion, and facilitated apoptosis. In addition, treatment with propofol efficiently reduced MMP‑2 protein expression levels, and overexpression of miR‑218 also decreased MMP‑2 protein expression levels. Whereas, neutralization of miR‑218 using the anti‑miR-218 antibody reversed the effects of propofol on the biological behavior of U373 cells, and on the inhibition of MMP-2 protein expression. In conclusion, propofol may effectively suppress proliferation and invasion, and induce the apoptosis of glioma cells, at least partially through upregulation of miR-218 expression.
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Affiliation(s)
- Jinquan Xu
- Department of Anesthesiology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang 321000, P.R. China
| | - Weiyun Xu
- Department of Anesthesiology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang 321000, P.R. China
| | - Jiaqun Zhu
- Department of Anesthesiology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang 321000, P.R. China
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Cata JP, Lasala J, Bugada D. Best practice in the administration of analgesia in postoncological surgery. Pain Manag 2015; 5:273-84. [PMID: 26072922 DOI: 10.2217/pmt.15.21] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The rationale for using multimodal analgesia after any major surgery is achievement of adequate analgesia while avoiding the unwanted effects of large doses of any analgesic, in particular opioids. There are two reasons why we can hypothesize that multimodal analgesia might have a significant impact on cancer-related outcomes in the context of oncological orthopedic surgery. First, because multimodal analgesia is a key component of enhanced-recovery pathways and can accelerate return to intended oncological therapy. And second, because some of the analgesic used in multimodal analgesia (i.e., COX inhibitors, local analgesics and dexamethasone) can induce apoptosis in cancer cells and/or diminish the inflammatory response during surgery which itself can facilitate tumor growth.
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Affiliation(s)
- Juan P Cata
- Department of Anesthesiology & Perioperative Medicine, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030, USA.,Anesthesia & Surgical Oncology Research Group
| | - Javier Lasala
- Department of Anesthesiology & Perioperative Medicine, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030, USA.,Anesthesia & Surgical Oncology Research Group
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Escribá PV, Busquets X, Inokuchi JI, Balogh G, Török Z, Horváth I, Harwood JL, Vígh L. Membrane lipid therapy: Modulation of the cell membrane composition and structure as a molecular base for drug discovery and new disease treatment. Prog Lipid Res 2015; 59:38-53. [PMID: 25969421 DOI: 10.1016/j.plipres.2015.04.003] [Citation(s) in RCA: 179] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 04/10/2015] [Accepted: 04/29/2015] [Indexed: 01/17/2023]
Abstract
Nowadays we understand cell membranes not as a simple double lipid layer but as a collection of complex and dynamic protein-lipid structures and microdomains that serve as functional platforms for interacting signaling lipids and proteins. Membrane lipids and lipid structures participate directly as messengers or regulators of signal transduction. In addition, protein-lipid interactions participate in the localization of signaling protein partners to specific membrane microdomains. Thus, lipid alterations change cell signaling that are associated with a variety of diseases including cancer, obesity, neurodegenerative disorders, cardiovascular pathologies, etc. This article reviews the newly emerging field of membrane lipid therapy which involves the pharmacological regulation of membrane lipid composition and structure for the treatment of diseases. Membrane lipid therapy proposes the use of new molecules specifically designed to modify membrane lipid structures and microdomains as pharmaceutical disease-modifying agents by reversing the malfunction or altering the expression of disease-specific protein or lipid signal cascades. Here, we provide an in-depth analysis of this emerging field, especially its molecular bases and its relevance to the development of innovative therapeutic approaches.
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Affiliation(s)
- Pablo V Escribá
- Department of Biology, University of the Balearic Islands, E-07122 Palma de Mallorca, Spain
| | - Xavier Busquets
- Department of Biology, University of the Balearic Islands, E-07122 Palma de Mallorca, Spain
| | - Jin-ichi Inokuchi
- Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan
| | - Gábor Balogh
- Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary
| | - Zsolt Török
- Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary
| | - Ibolya Horváth
- Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary
| | - John L Harwood
- School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK.
| | - László Vígh
- Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
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Cassinello F, Prieto I, del Olmo M, Rivas S, Strichartz GR. Cancer surgery: how may anesthesia influence outcome? J Clin Anesth 2015; 27:262-72. [PMID: 25769963 DOI: 10.1016/j.jclinane.2015.02.007] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 12/12/2014] [Accepted: 02/17/2015] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To review the published literature regarding the effects of anesthesia on cancer surgery to prevent tumor cell proliferation/migration or induce apoptosis. BACKGROUND Surgery is the main treatment for potentially curable solid tumors, but most cancer-related deaths in patients who have received previous surgical treatment are caused by metastatic disease. There is increasing evidence that anesthetic technique has the potential to affect long-term outcome after cancer surgery. METHODS This work reviews the English published literature that was obtained by performing a search of the PubMed database up to January 2014. We selected articles that provided evidence or reviewed the possible actions of anesthetics on cancer cells or the influence of anesthesia in recurrence/outcome. RESULTS Inhaled anesthetics induce immunosuppression and activate inflammatory cascade activation, whereas propofol has a protective action. Opioids might promote cancer recurrence and metastasis. In vitro and in vivo studies have demonstrated that local anesthetics inhibit proliferation and migration of cancer cells and induce apoptosis. CONCLUSIONS Anesthesiologists should follow current best clinical practice and include all strategies that effectively decrease pain and attenuate stress. Regional anesthesia and multimodal analgesia, adding anti-inflammatory drugs, play an unquestionable role in the control of perioperative pain and may improve recurrence-free survival.
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Affiliation(s)
| | - Isabel Prieto
- IDC-Salud Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain.
| | - Mercedes del Olmo
- IDC-Salud Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain
| | - Sonia Rivas
- IDC-Salud Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain
| | - Gary R Strichartz
- Pain Research Center, Department of Anesthesia. Harvard Medical School, Brigham and Women's Hospital, Boston, 02115 MA, USA
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48
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Biophysical Interactions of Novel Oleic Acid Conjugate and its Anticancer Potential in HeLa Cells. J Fluoresc 2015; 25:519-25. [DOI: 10.1007/s10895-015-1512-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 01/19/2015] [Indexed: 10/24/2022]
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Harvey KA, Xu Z, Saaddatzadeh MR, Wang H, Pollok K, Cohen-Gadol AA, Siddiqui RA. Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines. J Neurosurg 2014; 122:547-56. [PMID: 25526274 DOI: 10.3171/2014.10.jns14759] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECT Glioblastoma is a rapidly infiltrating tumor that consistently rematerializes despite various forms of aggressive treatment. Brain tumors are commonly treated with alkylating drugs, such as lomustine, which are chemotherapeutic agents. Use of these drugs, however, is associated with serious side effects. To reduce the side effects, one approach is to combine lower doses of chemotherapeutic drugs with other nontoxic anticancer agents. In this study, using glioblastoma cell lines, the authors investigated the anticancer effects of lomustine, alone and in combination with docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid normally abundant in the brain and known for its anticancer potential. METHODS Cells were cultured from 3 human-derived tumor cell lines (U87-MG, DB029, and MHBT161) and supplemented with either DHA or lomustine to determine the growth inhibitory potential using WST-1, a mitochondrial functional indicator. Human-derived cerebral cortex microvascular endothelial cells served as a normal phenotypic control. Cellular incorporation of DHA was analyzed by gas chromatography. Using flow cytometric analysis, the DHA and/or lomustine effect on induction of apoptosis and/or necrosis was quantified; subsequently, the DHA and lomustine effect on cell cycle progression was also assessed. Western blot analysis confirmed the role of downstream cellular targets. RESULTS U87-MG growth was inhibited with the supplementation of either DHA (ED50 68.3 μM) or lomustine (ED50 68.1 μM); however, growth inhibition was enhanced when U87-MG cells were administered equimolar doses of each compound, resulting in nearly total growth inhibition at 50 μM. Gas chromatography analysis of the fatty acid profile in DHA-supplemented U87-MG cells resulted in a linear dose-dependent increase in DHA incorporation (< 60 μM). The combination of DHA and lomustine potently induced U87-MG apoptosis and necrosis as indicated by flow cytometric analysis. Activation of caspase-3 and poly (ADP-ribose) polymerase (PARP) was evident in lomustine-treated U87-MG cells, although this activation did not appear to be dependent on DHA supplementation. Additionally, lomustine-treated cells' growth arrested in the G2/M cell cycle stage, regardless of the presence of DHA. Similar to the U87-MG observations, the combination of DHA and lomustine resulted in growth inhibition of 2 additional human-derived glioblastoma cell lines, DB029 and MHBT161. Importantly, in primary human-derived cerebral cortex endothelial cells, this combination was only growth inhibitory (40.8%) at the highest dose screened (100 μM), which indicates a certain degree of selectivity toward glioblastoma. CONCLUSIONS Taken together, these data suggest a potential role for a combination therapy of lomustine and DHA for the treatment of glioblastomas.
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Affiliation(s)
- Kevin A Harvey
- Cellular Biochemistry Laboratory, Indiana University Health Methodist Research Institute
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Song J, Shen Y, Zhang J, Lian Q. Mini profile of potential anticancer properties of propofol. PLoS One 2014; 9:e114440. [PMID: 25502773 PMCID: PMC4263663 DOI: 10.1371/journal.pone.0114440] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2014] [Accepted: 11/07/2014] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Propofol (2, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS This study aimed to establish a profile to quantitatively and functionally evaluate the anticancer properties of propofol in three cancer cell lines: non-small cell lung carcinoma cell line A549, human colon carcinoma cell line LoVo, and human breast cancer cell line SK-BR-3. We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells. However, there was no change in caspase-3 expression in SK-BR-3 cells. High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment. BAX, a major protein that promotes apoptosis in the regulation phase, was highly expressed in A549 cells after treatment with 25 µM propofol. Apoptosis induced by propofol may be associated with cancer cells carrying Kras mutations. CONCLUSIONS/SIGNIFICANCE Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status. Only Kras mutation in Codon 12 instead of other Kras status has been demonstrated to play an important role in sensitizing the propofol-induced apoptosis in cancer cell lines from our study. These findings may enable us a detailed investigation of propofol/Kras-mediated cancer cell apoptosis in the future.
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Affiliation(s)
- Jing Song
- Department of Anesthesiology, Montefiore Medical Center, New York, New York, United States of America
- * E-mail:
| | - Yenji Shen
- Department of Anesthesiology, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jing Zhang
- Department of Anesthesiology, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qingquan Lian
- Department of Anesthesiology, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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