|
1
|
Liu S, Wang B, Chen T, Wang H, Liu J, Zhao X, Zhang Y. Two new and effective food-extracted immunomodulatory agents exhibit anti-inflammatory response activity in the hACE2 acute lung injury murine model of COVID-19. Front Immunol 2024; 15:1374541. [PMID: 38807598 PMCID: PMC11130445 DOI: 10.3389/fimmu.2024.1374541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/25/2024] [Indexed: 05/30/2024] Open
Abstract
OBJECTIVE The coronavirus disease 2019 (COVID-19) spread rapidly and claimed millions of lives worldwide. Acute respiratory distress syndrome (ARDS) is the major cause of COVID-19-associated deaths. Due to the limitations of current drugs, developing effective therapeutic options that can be used rapidly and safely in clinics for treating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is necessary. This study aims to investigate the effects of two food-extracted immunomodulatory agents, ajoene-enriched garlic extract (AGE) and cruciferous vegetables-extracted sulforaphane (SFN), on anti-inflammatory and immune responses in a SARS-CoV-2 acute lung injury mouse model. METHODS In this study, we established a mouse model to mimic the SARS-CoV-2 infection acute lung injury model via intratracheal injection of polyinosinic:polycytidylic acid (poly[I:C]) and SARS-CoV-2 recombinant spike protein (SP). After the different agents treatment, lung sections, bronchoalveolar lavage fluid (BALF) and fresh faeces were harvested. Then, H&E staining was used to examine symptoms of interstitial pneumonia. Flow cytometry was used to examine the change of immune cell populations. Multiplex cytokines assay was used to examine the inflammatory cytokines.16S rDNA high-throughput sequencing was used to examine the change of gut microbiome. RESULTS Our results showed that AGE and SFN significantly suppressed the symptoms of interstitial pneumonia, effectively inhibited the production of inflammatory cytokines, decreased the percentage of inflammatory cell populations, and elevated T cell populations in the mouse model. Furthermore, we also observed that the gut microbiome of genus Paramuribaculum were enriched in the AGE-treated group. CONCLUSION Here, for the first time, we observed that these two novel, safe, and relatively inexpensive immunomodulatory agents exhibited the same effects on anti-inflammatory and immune responses as neutralizing monoclonal antibodies (mAbs) against interleukin 6 receptor (IL-6R), which have been suggested for treating COVID-19 patients. Our results revealed the therapeutic ability of these two immunomodulatory agents in a mouse model of SARS-CoV-2 acute lung injury by promoting anti-inflammatory and immune responses. These results suggest that AGE and SFN are promising candidates for the COVID-19 treatment.
Collapse
Affiliation(s)
- Shasha Liu
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Baiqiao Wang
- The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Tianran Chen
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hui Wang
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jinbo Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, China
| | - Xuan Zhao
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yi Zhang
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- School of Life Sciences, Zhengzhou University, Zhengzhou, China
- School of Public Health, Zhengzhou University, Zhengzhou, China
- Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, China
| |
Collapse
|
|
2
|
Cho Y, Hwang JW, Park NJ, Moon J, Ali KH, Seo YH, Kim IS, Kim SN, Kim YK. SPC-180002, a SIRT1/3 dual inhibitor, impairs mitochondrial function and redox homeostasis and represents an antitumor activity. Free Radic Biol Med 2023; 208:73-87. [PMID: 37536458 DOI: 10.1016/j.freeradbiomed.2023.07.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/12/2023] [Accepted: 07/31/2023] [Indexed: 08/05/2023]
Abstract
Since sirtuins (SIRTs) are closely associated with reactive oxygen species (ROS) and antioxidant system, the development of their selective inhibitors is drawing attention for understanding of cellular redox homeostasis. Here, we describe the pharmacological properties of SPC-180002, which incorporates a methyl methacrylate group as a key pharmacophore, along with its comprehensive molecular mechanism as a novel dual inhibitor of SIRT1/3. The dual inhibition of SIRT1/3 by SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. Increased p21 interacts with and inhibits CDK, thereby interfering with cell cycle progression. SPC-180002 leads to mitochondrial dysfunction by inhibiting mitophagy, which is accompanied by a reduction in oxygen consumption rate. Consequently, SPC-180002 strongly suppresses the proliferation of cancer cells and exerts anticancer effect in vivo. Taken together, the novel SIRT1/3 dual inhibitor, SPC-180002, impairs mitochondrial function and redox homeostasis, thereby strongly inhibiting cell cycle progression and cancer cell growth.
Collapse
Affiliation(s)
- Yena Cho
- Muscle Physiome Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Jee Won Hwang
- Muscle Physiome Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - No-June Park
- Natural Product Research Institute, Korea Institute of Science and Technology, Gangneung, 25451, Republic of Korea; Division of Bio-Medical Science and Technology, University of Science and Technology KIST School, Seoul, 02792, Republic of Korea
| | - Junghyea Moon
- School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Khan Hashim Ali
- College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea
| | - Young Ho Seo
- College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea
| | - In Su Kim
- School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
| | - Su-Nam Kim
- Natural Product Research Institute, Korea Institute of Science and Technology, Gangneung, 25451, Republic of Korea; Division of Bio-Medical Science and Technology, University of Science and Technology KIST School, Seoul, 02792, Republic of Korea.
| | - Yong Kee Kim
- Muscle Physiome Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
| |
Collapse
|
|
3
|
Jeong A, Cho Y, Cho M, Bae GU, Song DG, Kim SN, Kim YK. PRMT7 Inhibitor SGC8158 Enhances Doxorubicin-Induced DNA Damage and Its Cytotoxicity. Int J Mol Sci 2022; 23:ijms232012323. [PMID: 36293180 PMCID: PMC9604017 DOI: 10.3390/ijms232012323] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 10/09/2022] [Accepted: 10/13/2022] [Indexed: 11/07/2022] Open
Abstract
Protein arginine methyltransferase 7 (PRMT7) regulates various cellular responses, including gene expression, cell migration, stress responses, and stemness. In this study, we investigated the biological role of PRMT7 in cell cycle progression and DNA damage response (DDR) by inhibiting PRMT7 activity with either SGC8158 treatment or its specific siRNA transfection. Suppression of PRMT7 caused cell cycle arrest at the G1 phase, resulting from the stabilization and subsequent accumulation of p21 protein. In addition, PRMT7 activity is closely associated with DNA repair pathways, including both homologous recombination and non-homologous end-joining. Interestingly, SGC8158, in combination with doxorubicin, led to a synergistic increase in both DNA damage and cytotoxicity in MCF7 cells. Taken together, our data demonstrate that PRMT7 is a critical modulator of cell growth and DDR, indicating that it is a promising target for cancer treatment.
Collapse
Affiliation(s)
- Ahyeon Jeong
- Muscle Physiome Research Center and Drug Information Research Institute, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Korea
| | - Yena Cho
- Muscle Physiome Research Center and Drug Information Research Institute, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Korea
| | - Minkyeong Cho
- Muscle Physiome Research Center and Drug Information Research Institute, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Korea
| | - Gyu-Un Bae
- Muscle Physiome Research Center and Drug Information Research Institute, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Korea
| | - Dae-Geun Song
- Natural Products Research Institute, KIST Gangneung, Gangneung 25451, Korea
| | - Su-Nam Kim
- Natural Products Research Institute, KIST Gangneung, Gangneung 25451, Korea
- Division of Bio-Medical Science and Technology, University of Science and Technology KIST School, Seoul 02792, Korea
- Correspondence: (S.-N.K.); (Y.K.K.); Tel.: +82-33-650-3503 (S.-N.K.); +82-2-2077-7688 (Y.K.K.)
| | - Yong Kee Kim
- Muscle Physiome Research Center and Drug Information Research Institute, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Korea
- Correspondence: (S.-N.K.); (Y.K.K.); Tel.: +82-33-650-3503 (S.-N.K.); +82-2-2077-7688 (Y.K.K.)
| |
Collapse
|
|
4
|
Yao M, Cai Y, Wu ZJ, Zhou P, Sai WL, Wang DF, Wang L, Yao DF. Effects of targeted-edited oncogenic insulin-like growth factor-1 receptor with specific-sgRNA on biological behaviors of HepG2 cells. World J Clin Cases 2022; 10:10017-10030. [PMID: 36246809 PMCID: PMC9561564 DOI: 10.12998/wjcc.v10.i28.10017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 04/28/2022] [Accepted: 08/25/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Insulin-like growth factor-1 receptor (IGF-1R) is over-expressed in hepatocellular carcinoma (HCC). However, the relationship between IGF-1R activation and HCC progression remains unidentified. AIM To investigate the effects of editing IGF-1R on the biological features of HCC cells. METHODS Immunohistochemistry analyzed the expressions of IGF-1R and P-glyco protein (P-gp) in HCC tissues and their distal non-cancerous tissues (non-Ca). IGF-1R was edited with Crispr/Cas9 system, screened specific sgRNAs, and then transfected into HepG2 cells. CCK-8, scratch wound test detected cell proliferation, migration, invasion and transwell assays, respectively. Alterations of IGF-1R and P-gp were confirmed by Western blotting. Alterations of anti-cancer drug IC50 values were analyzed at the cell level. RESULTS The positive rates of IGF-1R (93.6%, χ 2 = 63.947) or P-gp (88.2%, χ2 = 58.448) were significantly higher (P < 0.001) in the HCC group than those (36.6% in IGF-1R or 26.9% in P-gp) in the non-Ca group. They were positively correlated between high IGF-1R and P-gp expression, and they were associated with hepatitis B virus infection and vascular invasion of HCC. Abnormal expressions of circulating IGF-1R and P-gp were confirmed and associated with HCC progression. Biological feature alterations of HCC cells transfected with specific sgRNA showed IGF-1R expression down-regulation, cell proliferation inhibition, cell invasion or migration potential decreasing, and enhancing susceptibility of HepG2 cells to anti-cancer drugs. CONCLUSION Edited oncogenic IGF-1R was useful to inhibit biological behaviors of HepG2 cells.
Collapse
Affiliation(s)
- Min Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Yin Cai
- Department of Oncology, Xinghua People’s Hospital, Xinghua 225700, Jiangsu Province, China
| | - Zhi-Jun Wu
- Department of Oncology, Affiliated Nantong Rehabilitation Hospital of Nantong University, Nantong 226002, Jiangsu Province, China
| | - Ping Zhou
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Li Sai
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - De-Feng Wang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Research Center for Intelligent Information Technology, Nantong University, Nantong 226019, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| |
Collapse
|
|
5
|
Li Y, Zu L, Wu H, Zhang F, Fan Y, Pan H, Du X, Guo F, Zhou Q. MiR-192/NKRF axis confers lung cancer cell chemoresistance to cisplatin via the NF-κB pathway. Thorac Cancer 2021; 13:430-441. [PMID: 34953057 PMCID: PMC8807278 DOI: 10.1111/1759-7714.14278] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 11/29/2021] [Accepted: 11/30/2021] [Indexed: 02/05/2023] Open
Abstract
Background Chemoresistance influences the therapeutic effect of cisplatin and remains a major obstacle to its clinical use. MicroRNAs are associated with drug resistance of various tumors. However, the association between microRNAs and cisplatin in lung cancer remains largely unclear. Methods MicroRNA expression profile was identified by microRNA microarray between the lung cancer cisplatin‐sensitive cell line A549 (A549) and cisplatin‐resistant cell line A549/DDP (A549/DDP) and confirmed by quantitative real‐time‐PCR (qRT‐PCR). In vitro loss‐ and gain‐of‐function studies were performed to reveal the biological function of miR‐192 and related mechanism of the microRNA‐192/NKRF axis in lung cancer cell cisplatin resistance. Results Increased miR‐192 expression was detected in A549/DDP cells compared to A549. High miR‐192 expression significantly suppressed apoptosis, enhanced proliferation, and conferred resistance to cisplatin in lung cancer cells. NF‐κB repressing factor (NKRF), which is involved in the regulation of the NF‐κB signaling pathway, was identified as a direct target of miR‐192. Overexpression of miR‐192 significantly increased the nuclear protein amount and transcriptional activation of NF‐κB and expression of cIAP1, cIAP2, Bcl‐xl and XIAP, whereas decreased miR‐192 expression did the opposite. Inhibition of the NF‐κB signal pathway by curcumin reversed the effect of upregulation of miR‐192 on proliferation, apoptosis and cisplatin‐resistance in lung cancer cells. These results indicated that miR‐192/ NKRF axis enhances the cisplatin resistance of lung cancer cells through activating the NF‐κB pathway in vitro. Conclusions MiR‐192 plays a crucial role in cisplatin‐resistance of lung cancer cells. Thus, MiR‐192 may represent a therapeutic target for overcoming resistance to cisplatin‐based chemotherapy in lung cancer.
Collapse
Affiliation(s)
- Yang Li
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Lingling Zu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Heng Wu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Fang Zhang
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yaguang Fan
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hongli Pan
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Xinxin Du
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Fengjie Guo
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Qinghua Zhou
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.,Sichuan Lung Cancer Institute, Sichuan Lung Cancer Center, West China Hospital, Chengdu, Sichuan University, China
| |
Collapse
|
|
6
|
A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells. Sci Rep 2021; 11:10822. [PMID: 34031528 PMCID: PMC8144389 DOI: 10.1038/s41598-021-90337-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 05/10/2021] [Indexed: 01/02/2023] Open
Abstract
The success of cancer chemotherapy is limited by multidrug resistance (MDR), which is mainly caused by P-glycoprotein (P-gp) overexpression. In the present study, we describe a novel microtubule inhibitor, 5-(N-methylmaleimid-3-yl)-chromone (SPC-160002), that can be used to overcome MDR. A synthetic chromone derivative, SPC-160002, showed a broad spectrum of anti-proliferative effects on various human cancer cells without affecting P-gp expression and its drug efflux function. Treatment with SPC-160002 arrested the cell cycle at the M phase, as evidenced using fluorescence-activated cell sorting analysis, and increased the levels of mitotic marker proteins, including cyclin B, pS10-H3, and chromosomal passenger complex. This mitotic arrest by SPC-160002 was mediated by promoting and stabilizing microtubule polymerization, similar to the mechanism observed in case of taxane-based drugs. Furthermore, SPC-160002 suppressed the growth and sphere-forming activity of cancer stem cells. Our data herein strongly suggest that SPC-160002, a novel microtubule inhibitor, can be used to overcome MDR and can serve as an attractive candidate for anticancer drugs.
Collapse
|
|
7
|
Yamamoto Raynbird M, Khokhar SS, Neef D, Evans GJS, Wirth T. Synthesis of Ajoene Analogues by Novel Synthetic Strategies. Chemistry 2021; 27:3008-3012. [PMID: 33283953 DOI: 10.1002/chem.202005023] [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: 11/19/2020] [Revised: 12/04/2020] [Indexed: 11/10/2022]
Abstract
Ajoene is a compound found in garlic extracts exhibiting a large range of biological activity. Novel ajoene analogues have been prepared in the search of compounds with superior bioactivity. Modifications include the alteration of the sulfoxide, the central alkene and the terminal allyl groups.
Collapse
Affiliation(s)
| | - Shaista S Khokhar
- Neem Biotech, Roseheyworth Business Park North, Abertillery, NP131SX, UK
| | - Daniel Neef
- Neem Biotech, Roseheyworth Business Park North, Abertillery, NP131SX, UK
| | - Gareth J S Evans
- Neem Biotech, Roseheyworth Business Park North, Abertillery, NP131SX, UK
| | - Thomas Wirth
- School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff, CF10 3AT, UK
| |
Collapse
|
|
8
|
Cho Y, Kim YK. Cancer Stem Cells as a Potential Target to Overcome Multidrug Resistance. Front Oncol 2020; 10:764. [PMID: 32582535 PMCID: PMC7280434 DOI: 10.3389/fonc.2020.00764] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 04/21/2020] [Indexed: 12/21/2022] Open
Abstract
Multidrug resistance (MDR), which is a significant impediment to the success of cancer chemotherapy, is attributable to various defensive mechanisms in cancer. Initially, overexpression of ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp) was considered the most important mechanism for drug resistance; hence, many investigators for a long time focused on the development of specific ABC transporter inhibitors. However, to date their efforts have failed to develop a clinically applicable drug, leaving only a number of problems. The concept of cancer stem cells (CSCs) has provided new directions for both cancer and MDR research. MDR is known to be one of the most important features of CSCs and thus plays a crucial role in cancer recurrence and exacerbation. Therefore, in recent years, research targeting CSCs has been increasing rapidly in search of an effective cancer treatment. Here, we review the drugs that have been studied and developed to overcome MDR and CSCs, and discuss the limitations and future perspectives.
Collapse
Affiliation(s)
| | - Yong Kee Kim
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, South Korea
| |
Collapse
|
|
9
|
An Appraisal of Developments in Allium Sulfur Chemistry: Expanding the Pharmacopeia of Garlic. Molecules 2019; 24:molecules24214006. [PMID: 31694287 PMCID: PMC6864437 DOI: 10.3390/molecules24214006] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 10/28/2019] [Accepted: 10/30/2019] [Indexed: 12/26/2022] Open
Abstract
Alliums and allied plant species are rich sources of sulfur compounds that have effects on vascular homeostasis and the control of metabolic systems linked to nutrient metabolism in mammals. In view of the multiple biological effects ascribed to these sulfur molecules, researchers are now using these compounds as inspiration for the synthesis and development of novel sulfur-based therapeutics. This research has led to the chemical synthesis and biological assessment of a diverse array of sulfur compounds representative of derivatives of S-alkenyl-l-cysteine sulfoxides, thiosulfinates, ajoene molecules, sulfides, and S-allylcysteine. Many of these synthetic derivatives have potent antimicrobial and anticancer properties when tested in preclinical models of disease. Therefore, the current review provides an overview of advances in the development and biological assessment of synthetic analogs of allium-derived sulfur compounds.
Collapse
|
|
10
|
Lee HJ, Jeong JH, Ryu JH. Anti-pancreatic cancer activity of Z-ajoene from garlic: An inhibitor of the Hedgehog/Gli/FoxM1 axis. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.03.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
11
|
Wang W, Chen M, Jin X, Li X, Yang Z, Lin H, Xu S. H 2S induces Th1/Th2 imbalance with triggered NF-κB pathway to exacerbate LPS-induce chicken pneumonia response. CHEMOSPHERE 2018; 208:241-246. [PMID: 29879557 DOI: 10.1016/j.chemosphere.2018.05.152] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 05/22/2018] [Accepted: 05/24/2018] [Indexed: 05/20/2023]
Abstract
H2S is one of the air pollutants, which can cause multiple organ damage to the body. H2S exposure will directly damage respiratory system and cause inflammatory reaction. In this experiment, the effect of H2S on LPS-induce chicken pneumonia is explored from the Th1/Th2 balance and the NF-κB pathway. 42-day-old broilers was selected as research object, exposed to exogenous H2S, received an intraperitoneal injection of LPS to establish inflammatory model on forty-second days. We carry out qRT-PCR and Western blot to detect the expression of cytokines secreted by Th1/Th2, PPAR-γ/HO-1 genes, NF-κB pathway genes and the downstream genes COX-2 and iNOS. We found the expression of IL-4, IL-6, TNF-α and IL-1β increased and that of IFN-γ decreased, which indicating the immune imbalance of Th1/Th2 was occurred and the level of PPAR-γ/HO-1 was significantly suppressed. In addition, the activation of I-κB-β and NF-κB genes with the degradation of I-κB-α indicated that NF-κB pathway has been activated, which accompanied with COX-2, PGE and iNOS increasing. These results suggested that H2S exposure can lead to Th1/Th2 immune imbalance, repress the anti-inflammatory effect of PPAR-γ/HO-1, and then activate NF-κB pathway-related genes and the downstream genes to aggravate pneumonia induced by LPS.
Collapse
Affiliation(s)
- Wei Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Menghao Chen
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Xi Jin
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Xiaojing Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Zijiang Yang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Hongjin Lin
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
| | - Shiwen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
| |
Collapse
|
|
12
|
Pandey MK, Gupta SC, Nabavizadeh A, Aggarwal BB. Regulation of cell signaling pathways by dietary agents for cancer prevention and treatment. Semin Cancer Biol 2017; 46:158-181. [PMID: 28823533 DOI: 10.1016/j.semcancer.2017.07.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 07/05/2017] [Accepted: 07/12/2017] [Indexed: 12/17/2022]
Abstract
Although it is widely accepted that better food habits do play important role in cancer prevention and treatment, how dietary agents mediate their effects remains poorly understood. More than thousand different polyphenols have been identified from dietary plants. In this review, we discuss the underlying mechanism by which dietary agents can modulate a variety of cell-signaling pathways linked to cancer, including transcription factors, nuclear factor κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), activator protein-1 (AP-1), β-catenin/Wnt, peroxisome proliferator activator receptor- gamma (PPAR-γ), Sonic Hedgehog, and nuclear factor erythroid 2 (Nrf2); growth factors receptors (EGFR, VEGFR, IGF1-R); protein Kinases (Ras/Raf, mTOR, PI3K, Bcr-abl and AMPK); and pro-inflammatory mediators (TNF-α, interleukins, COX-2, 5-LOX). In addition, modulation of proteasome and epigenetic changes by the dietary agents also play a major role in their ability to control cancer. Both in vitro and animal based studies support the role of dietary agents in cancer. The efficacy of dietary agents by clinical trials has also been reported. Importantly, natural agents are already in clinical trials against different kinds of cancer. Overall both in vitro and in vivo studies performed with dietary agents strongly support their role in cancer prevention. Thus, the famous quote "Let food be thy medicine and medicine be thy food" made by Hippocrates 25 centuries ago still holds good.
Collapse
Affiliation(s)
- Manoj K Pandey
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
| | - Subash C Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Ali Nabavizadeh
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
| | | |
Collapse
|
|
13
|
Cheng QL, Li HL, Li YC, Liu ZW, Guo XH, Cheng YJ. CRA(Crosolic Acid) isolated from Actinidia valvata Dunn.Radix induces apoptosis of human gastric cancer cell line BGC823 in vitro via down-regulation of the NF-κB pathway. Food Chem Toxicol 2017; 105:475-485. [DOI: 10.1016/j.fct.2017.05.021] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Revised: 05/02/2017] [Accepted: 05/11/2017] [Indexed: 12/27/2022]
|
|
14
|
Vlahopoulos SA. Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode. Cancer Biol Med 2017; 14:254-270. [PMID: 28884042 PMCID: PMC5570602 DOI: 10.20892/j.issn.2095-3941.2017.0029] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The role of the transcription factor NF-κB in shaping the cancer microenvironment is becoming increasingly clear. Inflammation alters the activity of enzymes that modulate NF-κB function, and causes extensive changes in genomic chromatin that ultimately drastically alter cell-specific gene expression. NF-κB regulates the expression of cytokines and adhesion factors that control interactions among adjacent cells. As such, NF-κB fine tunes tissue cellular composition, as well as tissues' interactions with the immune system. Therefore, NF-κB changes the cell response to hormones and to contact with neighboring cells. Activating NF-κB confers transcriptional and phenotypic plasticity to a cell and thereby enables profound local changes in tissue function and composition. Research suggests that the regulation of NF-κB target genes is specifically altered in cancer. Such alterations occur not only due to mutations of NF-κB regulatory proteins, but also because of changes in the activity of specific proteostatic modules and metabolic pathways. This article describes the molecular mode of NF-κB regulation with a few characteristic examples of target genes.
Collapse
Affiliation(s)
- Spiros A Vlahopoulos
- The First Department of Pediatrics, University of Athens, Horemeio Research Laboratory, Athens 11527, Greece
| |
Collapse
|