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Kumari S, Peela S, Nagaraju GP, Srilatha M. Polysaccharides as therapeutic vehicles in pancreatic cancer. Drug Discov Today 2025; 30:104320. [PMID: 40024518 DOI: 10.1016/j.drudis.2025.104320] [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: 01/20/2025] [Revised: 02/13/2025] [Accepted: 02/25/2025] [Indexed: 03/04/2025]
Abstract
Pancreatic cancer (PC) is highly aggressive, with rising incidence and mortality rates. It has significant therapy obstacles due to the limited clinical options, late-stage identification, dense tumor microenvironment (TME), and resistance to therapy. Recent advances might improve treatment consequences in therapy strategies that target important TME components. Moreover, new polymeric drug delivery techniques based on polysaccharides such as polymeric micelles, liposomes, and nanoparticles enhance the solubility of drugs, drug stability, and tumor-specific targeting, which increase the chances of circumventing resistance and improving the efficacy of treatment. Preclinical research has suggested that by modulating the TME and enhancing the efficacy of chemotherapy, polysaccharide-based therapy, such as RP02-1 and DPLL-functionalized amylose, may help treat PC.
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Affiliation(s)
- Seema Kumari
- Department of Biotechnology, Dr. B.R. Ambedkar University, Srikakulam 532410 AP, India
| | - Sujatha Peela
- Department of Biotechnology, Dr. B.R. Ambedkar University, Srikakulam 532410 AP, India
| | - Ganji Purnachandra Nagaraju
- School of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Mundla Srilatha
- Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502, India.
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2
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Yang JL, Yang J, Fang RF, Sai WL, Yao DF, Yao M. Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma. World J Hepatol 2024; 16:1480-1492. [DOI: 10.4254/wjh.v16.i12.1480] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/22/2024] [Accepted: 09/13/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Angiopoietin-2 (Ang-2) level is related to hepatocellular carcinoma (HCC) progression. However, the dynamic expression and regulatory mechanism of Ang-2 remain unclear.
AIM To investigate Ang-2 levels in chronic liver diseases and validate early monitoring value with a dynamic model in hepatocarcinogenesis.
METHODS Sprague-Dawley rats in hepatocarcinogenesis were induced with diet 2-fluorenylacet-amide, and grouped based on liver histopathology by hematoxylin and eosin staining. Differently expressed genes or Ang-2 mRNA in livers were analyzed by whole-genome microarray. Ang-2 levels in chronic liver diseases were detected by an enzyme-linked immunosorbent assay.
RESULTS Clinical observation reveled that the circulating levels of Ang-2 and hypoxia-inducible factor-1α (HIF-1α) in patients with chronic liver diseases were progressively increased from benign to HCC (P < 0.001). Dynamic model validated that the up-regulated Ang-2 in liver and blood was positively correlated with HIF-1α in hepatocarcinogenesis (P < 0.001). Mechanistically, Ang-2 was regulated by HIF-1α. When specific HIF-1α- microRNAs transfected into HCC cells, the cell proliferation significantly inhibited, HIF-1α and Ang-2 down-regulated, and also affected epithelial-mesenchymal transition via increasing E-cadherin to block cell invasion or migration with reducing of snail, twist and vimentin.
CONCLUSION Hypoxia-induced Ang-2 up-regulating expression might serve as a sensitive early monitoring biomarker for hepatocarcinogenesis or HCC metastasis.
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Affiliation(s)
- Jun-Ling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Jie Yang
- Department of Biology, Life Science School of Nantong University, Nantong 226009, Jiangsu Province, China
| | - Rong-Fei Fang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Li Sai
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Min Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
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3
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Yan Z, Chen HQ. Anti-liver cancer effects and mechanisms and its application in nano DDS of polysaccharides: A review. Int J Biol Macromol 2024; 279:135181. [PMID: 39218183 DOI: 10.1016/j.ijbiomac.2024.135181] [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: 05/13/2024] [Revised: 07/23/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024]
Abstract
Liver cancer is the third leading cause of cancer death, with high incidence and poor treatment effect. In recent years, polysaccharides have attracted more and more attention in the research field of anti-liver cancer because of their high efficiency, low toxicity, good biocompatibility, wide sources and low cost. Polysaccharides have been proven to have good anti-liver cancer activity. In this paper, the pathways and molecular mechanisms of polysaccharides against liver cancer were reviewed in detail. Polysaccharides exert anti-liver cancer activity by blocking cell cycle, inducing apoptosis, regulating immunity, inhibiting cancer cell metastasis, inhibiting tumor angiogenesis and so on. The primary structure and chain conformation of polysaccharides have an important influence on their anti-liver cancer activity. Structural modification enhanced the anti-liver cancer activity of polysaccharides. Polysaccharides have good attenuated and synergistic effects on chemotherapy drugs. Polysaccharides can be used as functional carriers to construct intelligent nano drug delivery systems (DDS) targeting liver cancer. This review can provide theoretical support for the further development and application of polysaccharides in the field of anti-liver cancer, and provide theoretical reference and clues for relevant researchers in food, nutrition, medicine and other fields.
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Affiliation(s)
- Zheng Yan
- School of Food and Biological Engineering, Hefei University of Technology, 420 Feicui Road, Hefei, Anhui 230601, PR China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, 420 Feicui Road, Hefei, Anhui 230601, PR China
| | - Han-Qing Chen
- School of Food and Biological Engineering, Hefei University of Technology, 420 Feicui Road, Hefei, Anhui 230601, PR China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, 420 Feicui Road, Hefei, Anhui 230601, PR China.
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Feng B, Lu Y, Zhang B, Zhu Y, Su Z, Tang L, Yang L, Wang T, He C, Li C, Zhao J, Zheng X, Zheng G. Integrated microbiome and metabolome analysis reveals synergistic efficacy of basil polysaccharide and gefitinib in lung cancer through modulation of gut microbiota and fecal metabolites. Int J Biol Macromol 2024; 281:135992. [PMID: 39414535 DOI: 10.1016/j.ijbiomac.2024.135992] [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: 03/25/2024] [Revised: 09/08/2024] [Accepted: 09/22/2024] [Indexed: 10/18/2024]
Abstract
Emerging evidence suggests that gut microbiota and its metabolites significantly influence the effectiveness of EGFR-TKIs (e.g., gefitinib, erlotinib) in lung cancer treatment. Plant polysaccharides can interact with gut microbiota, leading to changes in the host-microbe metabolome that may affect drug metabolism and therapeutic outcomes. Our previous research demonstrated the efficacy of basil polysaccharide (BPS) in treating various cancers by regulating hypoxic microenvironment and inhibiting epithelial-mesenchymal transition process. However, the potential impact of BPS on gut microbiota has not been thoroughly explored. In this study, we employed an immunodeficient gefitinib-resistant xenograft mouse model to explore whether BPS enhances the antitumor effects of gefitinib. A multi-omics approach, including 16S rDNA amplicon sequencing and LC-MS, was used to elucidate these synergistic effects. Our findings indicate that BPS can enhance tumor responsiveness to gefitinib by modulating the gut microbiota and its metabolites through multiple metabolic pathways. These changes in gut microbiota and metabolites could potentially affect cancer related signaling pathway and lung resistance-related protein, which are pivotal in determining the efficacy of EGFR-TKIs in cancer treatment.
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Affiliation(s)
- Bing Feng
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Yanjing Lu
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Bowen Zhang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Ying Zhu
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Zuqing Su
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Lipeng Tang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Laijun Yang
- Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Tong Wang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Chunxia He
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Chutian Li
- Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China
| | - Jie Zhao
- Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China
| | - Xirun Zheng
- Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China
| | - Guangjuan Zheng
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
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Chen JH, Lin TH, Chien YC, Chen CY, Lin CT, Kuo WW, Chang WC. Aqueous Extracts of Ocimum gratissimum Sensitize Hepatocellular Carcinoma Cells to Cisplatin through BRCA1 Inhibition. Int J Mol Sci 2024; 25:8424. [PMID: 39125994 PMCID: PMC11313253 DOI: 10.3390/ijms25158424] [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: 06/15/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Ocimum gratissimum (O. gratissimum), a medicinal herb with antifungal and antiviral activities, has been found to prevent liver injury and liver fibrosis and induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we evaluated the effect of aqueous extracts of O. gratissimum (OGE) on improving the efficacy of chemotherapeutic drugs in HCC cells. Proteomic identification and functional assays were used to uncover the critical molecules responsible for OGE-induced sensitization mechanisms. The antitumor activity of OGE in combination with a chemotherapeutic drug was evaluated in a mouse orthotopic tumor model, and serum biochemical tests were further utilized to validate liver function. OGE sensitized HCC cells to the chemotherapeutic drug cisplatin. Proteomic analysis and Western blotting validation revealed the sensitization effect of OGE, likely achieved through the inhibition of breast cancer type 1 susceptibility protein (BRCA1). Mechanically, OGE treatment resulted in BRCA1 protein instability and increased proteasomal degradation, thereby synergistically increasing cisplatin-induced DNA damage. Moreover, OGE effectively inhibited cell migration and invasion, modulated epithelial-to-mesenchymal transition (EMT), and impaired stemness properties in HCC cells. The combinatorial use of OGE enhanced the efficacy of cisplatin and potentially restored liver function in a mouse orthotopic tumor model. Our findings may provide an alternate approach to improving chemotherapy efficacy in HCC.
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Affiliation(s)
- Jing-Huei Chen
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan; (J.-H.C.); (Y.-C.C.)
| | - Tsai-Hui Lin
- Department of Chinese Medicine, China Medical University Hospital, Taichung 404327, Taiwan;
| | - Yu-Chuan Chien
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan; (J.-H.C.); (Y.-C.C.)
| | - Chung-Yu Chen
- Research Center for Cancer Biology, China Medical University, Taichung 406040, Taiwan; (C.-Y.C.); (C.-T.L.)
| | - Chih-Tung Lin
- Research Center for Cancer Biology, China Medical University, Taichung 406040, Taiwan; (C.-Y.C.); (C.-T.L.)
| | - Wei-Wen Kuo
- Program for Biotechnology Industry, China Medical University, Taichung 406040, Taiwan
| | - Wei-Chao Chang
- Center for Molecular Medicine, China Medical University Hospital, Taichung 406040, Taiwan
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Wei X, Luo D, Li H, Li Y, Cen S, Huang M, Jiang X, Zhong G, Zeng W. The roles and potential mechanisms of plant polysaccharides in liver diseases: a review. Front Pharmacol 2024; 15:1400958. [PMID: 38966560 PMCID: PMC11222613 DOI: 10.3389/fphar.2024.1400958] [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: 03/14/2024] [Accepted: 05/30/2024] [Indexed: 07/06/2024] Open
Abstract
Plant polysaccharides (PP) demonstrate a diverse array of biological and pharmacological properties. This comprehensive review aims to compile and present the multifaceted roles and underlying mechanisms of plant polysaccharides in various liver diseases. These diseases include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), fibrosis, drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). This study aims to elucidate the intricate mechanisms and therapeutic potential of plant polysaccharides, shedding light on their significance and potential applications in the management and potential prevention of these liver conditions. An exhaustive literature search was conducted for this study, utilizing prominent databases such as PubMed, Web of Science, and CNKI. The search criteria focused on the formula "(plant polysaccharides liver disease) NOT (review)" was employed to ensure the inclusion of original research articles up to the year 2023. Relevant literature was extracted and analyzed from these databases. Plant polysaccharides exhibit promising pharmacological properties, particularly in the regulation of glucose and lipid metabolism and their anti-inflammatory and immunomodulatory effects. The ongoing progress of studies on the molecular mechanisms associated with polysaccharides will offer novel therapeutic strategies for the treatment of chronic liver diseases (CLDs).
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Affiliation(s)
- Xianzhi Wei
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou, China
| | - Daimin Luo
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Haonan Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Yagang Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou, China
| | - Shizhuo Cen
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou, China
| | - Min Huang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou, China
| | - Xianxing Jiang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Guoping Zhong
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou, China
| | - Weiwei Zeng
- Shenzhen Longgang Second People’s Hospital, Shenzhen, China
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7
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Cai Y, Guo J, Kang Y. Future prospect of polysaccharide as a potential therapy in hepatocellular carcinoma: A review. Int J Biol Macromol 2024; 270:132300. [PMID: 38735616 DOI: 10.1016/j.ijbiomac.2024.132300] [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: 10/23/2023] [Revised: 04/23/2024] [Accepted: 05/10/2024] [Indexed: 05/14/2024]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. A variety of new agents are in development for the treatment of the disease. Polysaccharide is important component of higher plants, membrane of the animal cell and the cell wall of microbes. It is also closely related to the physiological functions. Recently, there has been growing interest in polysaccharides as bioactive natural products, particularly in treating HCC. This paper provides a review of recent experimental and clinical studies on the effects and potential applications of polysaccharides in HCC treatment, aiming to offer theoretical insights and inspiration for further research on the bioactivity mechanisms of polysaccharides in HCC treatment.
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Affiliation(s)
- Yue Cai
- School of medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Jing Guo
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yongbo Kang
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China.
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He C, Li L, Feng B, Xie L, Zhang L, Liu B. Complete Response of Locally Advanced Lung Adenocarcinoma Following Basil Combined With Cisplatin Plus Pemetrexed Chemotherapy: A Case Report. Integr Cancer Ther 2024; 23:15347354241295269. [PMID: 39511726 PMCID: PMC11544759 DOI: 10.1177/15347354241295269] [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: 07/03/2024] [Revised: 09/01/2024] [Accepted: 10/11/2024] [Indexed: 11/15/2024] Open
Abstract
Concurrent chemoradiotherapy (CCRT) represents the established therapeutic modality for managing locally advanced non-small cell lung cancer (LA-NSCLC). However, its impact on improving the poor prognosis of LA-NSCLC patients is limited, and it can cause severe side effects. A 62-year-old Chinese female was diagnosed with unresectable stage IIIA lung adenocarcinoma. She refused CCRT. Enhanced computed tomography of the chest revealed a space-occupying lesion in her left pulmonary hilum, invading and encircling the pulmonary artery trunk. Due to the reported anti-tumor effects of basil, a stasis-removing Chinese herb, the patient received basil combined with cisplatin plus pemetrexed (CP) chemotherapy as first-line treatment. After 6 cycles of treatment, her condition achieved complete remission, and circulating tumor cells were reduced to zero. Regular follow-ups showed that the patient maintained progression-free survival for nearly 3 years. This case highlights the potential efficacy of basil combined with CP chemotherapy in treating LA-NSCLC. However, the curative effect of this regimen needs further validation through larger clinical trials.
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Affiliation(s)
- Chunxia He
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Liuning Li
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Bing Feng
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Liqian Xie
- Guangzhou University of Chinese Medicine, Baiyun District, Guangzhou, Guangdong Province, China
| | - Liwen Zhang
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Bai Liu
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
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Wang D, Zhang Z, Zhao L, Yang L, Lou C. Recent advances in natural polysaccharides against hepatocellular carcinoma: A review. Int J Biol Macromol 2023; 253:126766. [PMID: 37689300 DOI: 10.1016/j.ijbiomac.2023.126766] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 08/26/2023] [Accepted: 09/04/2023] [Indexed: 09/11/2023]
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor of the digestive system that poses a serious threat to human life and health. Chemotherapeutic drugs commonly used in the clinic have limited efficacy and heavy adverse effects. Therefore, it is imperative to find effective and safe alternatives, and natural polysaccharides (NPs) fit the bill. This paper summarizes in detail the anti-HCC activity of NPs in vitro, animal and clinical trials. Furthermore, the addition of NPs can reduce the deleterious effects of chemotherapeutic drugs such as immunotoxicity, bone marrow suppression, oxidative stress, etc. The potential mechanisms are related to induction of apoptosis and cell cycle arrest, block of angiogenesis, invasion and metastasis, stimulation of immune activity and targeting of MircoRNA. And on this basis, we further elucidate that the anti-HCC activity may be related to the monosaccharide composition, molecular weight (Mw), conformational features and structural modifications of NPs. In addition, due to its good physicochemical properties, it is widely used as a drug carrier in the delivery of chemotherapeutic drugs and small molecule components. This review provides a favorable theoretical basis for the application of the anti-HCC activity of NPs.
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Affiliation(s)
- Dazhen Wang
- Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - Zhengfeng Zhang
- Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - Lu Zhao
- Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - Liu Yang
- Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - ChangJie Lou
- Harbin Medical University Cancer Hospital, Harbin 150081, China.
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10
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Yousef EH, El-Magd NFA, El Gayar AM. Norcantharidin potentiates sorafenib antitumor activity in hepatocellular carcinoma rat model through inhibiting IL-6/STAT3 pathway. Transl Res 2023; 260:69-82. [PMID: 37257560 DOI: 10.1016/j.trsl.2023.05.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 05/19/2023] [Accepted: 05/23/2023] [Indexed: 06/02/2023]
Abstract
In hepatocellular carcinoma (HCC), sorafenib (Sora) efficacy is limited by primary and/or acquired resistance. Emerging evidence shows that the inflammatory factor interleukin 6 (IL-6) plays a role in Sora resistance. Norcantharidin (NCTD), a derivative of cantharidine, was identified as a potent IL-6 inhibitor. Thus, in this study, we evaluated NCTD ability to improve the Sora efficacy in HCC and its underlying molecular mechanisms. Male Sprague Dawely rats were administered NCTD (0.1 mg/kg/day; orally) or Sora (10 mg/kg day; orally) or combination for 6 weeks after HCC induction using thioacetamide (200 mg/kg; ip; 2 times/wk) for 16 weeks. Our results showed that NCTD greatly enhanced Sora activity against HCC and potentiated Sora-induced oxidative stress. NCTD enhanced Sora-induced tumor immunity reactivation by decreasing both fibrinogen-like protein 1 level and increasing both tumor necrosis factor-α gene expression along with CD8+ T cells number. Also, NCTD augmented Sora attenuation activity against TAA-induced angiogenesis and metastasis by decreasing VEGFA, HIF-1α, serum lactate dehydrogenase enzyme, and vimentin levels. The combined use of NCTD/Sora suppressed drug resistance and stemness by downregulating ATP-binding cassette subfamily G member 2, neurogenic locus notch homolog protein, spalt-like transcription factor 4, and CD133. NCTD boosted Sora antiproliferative and apoptotic activities by decreasing Ccnd1 and BCL2 expressions along with increasing BAX and caspase-3 expressions. To our knowledge, this study represents the first study providing evidence for the potential novel therapeutic use of NCTD/Sora combination for HCC. Moreover, no previous studies have reported the effect of NCTD on FGL1.
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Affiliation(s)
- Eman H Yousef
- Biochemistry department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Biochemistry department, Faculty of Pharmacy, Horus University-Egypt, Damietta, Egypt.
| | - Nada F Abo El-Magd
- Biochemistry department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Amal M El Gayar
- Biochemistry department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
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11
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Wei Y, Ke W, Lu Z, Ren Y. PI3K δ inhibitor PI-3065 induces apoptosis in hepatocellular carcinoma cells by targeting survivin. Chem Biol Interact 2023; 371:110343. [PMID: 36623716 DOI: 10.1016/j.cbi.2023.110343] [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: 09/20/2022] [Revised: 11/17/2022] [Accepted: 01/05/2023] [Indexed: 01/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and its clinical treatment remains challenging. The development of new treatment regimens is important for effective HCC treatment. Phosphoinositide 3-kinase (PI3K) is a lipid kinase that plays an important role in cell growth and metabolism and is overexpressed in nearly 50% of patients with HCC. Studies have shown that PI-3065, a small-molecule inhibitor of phosphatidylinositol 3-kinase delta, significantly inhibits solid breast cancer. However, its antitumor effects against HCC and the underlying mechanisms remain unclear. In the present study, we found that PI-3065 dose- and time-dependently reduced HCC cell viability and induced apoptosis while posing no obvious apoptotic toxicity in normal liver cells. Further mechanistic analysis showed that PI-3065 induced apoptosis mainly by inhibiting survivin protein expression, decreasing mitochondrial membrane potential, and promoting cytochrome C release. Simultaneously, PI-3065 markedly suppressed the colony formation, migration, and epithelial-mesenchymal transition abilities of HCC cells. Furthermore, transplantation of nude mice with HCC tumors showed that PI-3065 inhibits HCC tumor growth in vivo by targeting survivin. In summary, PI-3065 specifically inhibited survivin expression and exerted anti-HCC activity in vivo and in vitro, suggesting that it may serve as an effective antitumor drug for HCC treatment, which warrants further study.
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Affiliation(s)
- Yuze Wei
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China
| | - Weiwei Ke
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Zaiming Lu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
| | - Ying Ren
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
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Systems Pharmacology-Based Strategy to Investigate the Mechanism of Ruangan Lidan Decoction for Treatment of Hepatocellular Carcinoma. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:2940654. [PMID: 36578460 PMCID: PMC9791079 DOI: 10.1155/2022/2940654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 12/23/2022]
Abstract
epatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide. Currently, the prevention and treatment of HCC remains a major challenge. As a traditional Chinese medicine (TCM) formula, Ruangan Lidan decoction (RGLD) has been proved to own the effect of relieving HCC symptoms. However, due to its biological effects and complex compositions, its underlying mechanism of actions (MOAs) have not been fully clarified yet. In this study, we proposed a pharmacological framework to systematically explore the MOAs of RGLD against HCC. We firstly integrated the active ingredients and potential targets of RGLD. We next highlighted 25 key targets that played vital roles in both RGLD and HCC disease via a protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, an ingredient-target network of RGLD consisting of 216 ingredients with 306 targets was constructed, and multilevel systems pharmacology analyses indicated that RGLD could act on multiple biological processes related to the pathogenesis of HCC, such as cellular response to hypoxia and cell proliferation. Additionally, integrated pathway analysis of RGLD uncovered that RGLD might treat HCC through regulating various pathways, including MAPK signaling pathway, PI3K/Akt signaling pathway, TNF signaling pathway, and ERBB signaling pathway. Survival analysis results showed that HCC patients with low expression of VEGFA, HIF1A, CASP8, and TOP2A were related with a higher survival rate than those with high expression, indicating the potential clinical significance for HCC. Finally, molecular docking results of core ingredients and targets further proved the feasibility of RGLD in the treatment of HCC. Overall, this study indicates that RGLD may treat HCC through multiple mechanisms, which also provides a potential paradigm to investigate the MOAs of TCM prescription.
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Gao S, Jiang X, Wang L, Jiang S, Luo H, Chen Y, Peng C. The pathogenesis of liver cancer and the therapeutic potential of bioactive substances. Front Pharmacol 2022; 13:1029601. [PMID: 36278230 PMCID: PMC9581229 DOI: 10.3389/fphar.2022.1029601] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 09/20/2022] [Indexed: 11/13/2022] Open
Abstract
Liver cancer is the third most common cause of cancer-related deaths in the world and has become an urgent problem for global public health. Bioactive substances are widely used for the treatment of liver cancer due to their widespread availability and reduced side effects. This review summarizes the main pathogenic factors involved in the development of liver cancer, including metabolic fatty liver disease, viral infection, and alcoholic cirrhosis, and focuses on the mechanism of action of bioactive components such as polysaccharides, alkaloids, phenols, peptides, and active bacteria/fungi. In addition, we also summarize transformation methods, combined therapy and modification of bioactive substances to improve the treatment efficiency against liver cancer, highlighting new ideas in this field.
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Affiliation(s)
- Song Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xingyue Jiang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Liang Wang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shanshan Jiang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hanyuan Luo
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yan Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Yan Chen, ; Cheng Peng,
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Yan Chen, ; Cheng Peng,
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14
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Yan H, Ma X, Mi Z, He Z, Rong P. Extracellular Polysaccharide from Rhizopus nigricans Inhibits Hepatocellular Carcinoma via miR-494-3p/TRIM36 Axis and Cyclin E Ubiquitination. J Clin Transl Hepatol 2022; 10:608-619. [PMID: 36062277 PMCID: PMC9396321 DOI: 10.14218/jcth.2021.00301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/11/2021] [Accepted: 10/27/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS This study was designed to uncover the mechanism for extracellular polysaccharide (EPS1-1)-mediated effects on hepatocellular carcinoma (HCC) development. METHODS HCC cells were treated with EPS1-1, miR-494-3p mimic, sh-TRIM36, and pcDNA3.1-TRIM36. The levels of miR-494-3p and TRIM36 were measured in normal hepatocytes, THLE-2, and HepG2 and HuH7HCC cell lines, along with the protein expression of cyclin D/E and p21. The proliferation, cell cycle, and apoptosis of HCC cells were assayed. The interactions between miR-494-3p and TRIM36, and between TRIM36 and cyclin E were assessed. Finally, the expression and localization of TRIM36 and cyclin E were monitored, and tumor apoptosis was detected, in tumor xenograft model. RESULTS EPS1-1 suppressed HCC cell proliferation and cyclin D/E expression and promoted apoptosis and p21 expression. miR-494-3p was upregulated and TRIM36 was downregulated in HCC cells. Transfection with miR-494-3p mimic or sh-TRIM36 facilitated HCC cell proliferation and the expression of cyclin D/E protein but they inhibited apoptosis and p21 expression in the presence of EPS1-1. Overexpression of TRIM36 further consolidated EPS1-1-mediated inhibition of HCC proliferation, cyclin D/E, and the promotion of apoptosis and p21 expression. Those effects were reversed by miR-494-3p overexpression. TRIM36 was a target gene of miR-494-3p, and TRIM36 induced cyclin E ubiquitination. EPS1-1 suppressed cyclin E expression, promoted TRIM36 expression and tumor apoptosis, all of which were abrogated by increasing the expression of miR-494-3p in vivo. CONCLUSIONS EPS1-1 protected against HCC by limiting its proliferation and survival through the miR-494-3p/TRIM36 axis and by inducing cyclin E ubiquitination.
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Affiliation(s)
| | | | | | | | - Pengfei Rong
- Correspondence to: Pengfei Rong, Department of Radiology, The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China. ORCID: https://orcid.org/0000-0001-5473-1982. Tel: +86-18684706350, Fax: +86-731-88618411, E-mail:
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15
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Cai C, Yang L, Zhou K. 8DEstablishment and validation of a hypoxia-related signature predicting prognosis in hepatocellular carcinoma. BMC Gastroenterol 2021; 21:463. [PMID: 34895169 PMCID: PMC8667367 DOI: 10.1186/s12876-021-02057-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 12/02/2021] [Indexed: 12/24/2022] Open
Abstract
Background Hypoxia plays a crucial role in immunotherapy of hepatocellular carcinoma (HCC) by changing the tumor microenvironment. Until now the association between hypoxia genes and prognosis of HCC remains obscure. We attempt to construct a hypoxia model to predict the prognosis in HCC.
Results We screened out 3 hypoxia genes (ENO1, UGP2, TPI1) to make the model, which can predict prognosis in HCC. And this model emerges as an independent prognostic factor for HCC. A Nomogram was drawn to evaluate the overall survival in a more accurate way. Furthermore, immune infiltration state and immunosuppressive microenvironment of the tumor were detected in high-risk patients. Conclusion We establish and validate a risk prognostic model developed by 3 hypoxia genes, which could effectively evaluate the prognosis of HCC patients. This prognostic model can be used as a guidance for hypoxia modification in HCC patients undergoing immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-02057-0.
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Affiliation(s)
- Congbo Cai
- Emergency Department of Yinzhou No.2 Hospital, Ningbo, 315000, Zhejiang, China
| | - Lei Yang
- Emergency Department of Yinzhou No.2 Hospital, Ningbo, 315000, Zhejiang, China
| | - Kena Zhou
- Gastroenterology Department of Ningbo No. 9 Hospital, Ningbo, 315000, Zhejiang, China.
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Dybka-Stępień K, Otlewska A, Góźdź P, Piotrowska M. The Renaissance of Plant Mucilage in Health Promotion and Industrial Applications: A Review. Nutrients 2021; 13:nu13103354. [PMID: 34684354 PMCID: PMC8539170 DOI: 10.3390/nu13103354] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/13/2022] Open
Abstract
Plant mucilage is a renewable and cost-effective source of plant-based compounds that are biologically active, biodegradable, biocompatible, nontoxic, and environmentally friendly. Until recently, plant mucilage has been of interest mostly for technological purposes. This review examined both its traditional uses and potential modern applications in a new generation of health-promoting foods, as well as in cosmetics and biomaterials. We explored the nutritional, phytochemical, and pharmacological richness of plant mucilage, with a particular focus on its biological activity. We also highlighted areas where more research is needed in order to understand the full commercial potential of plant mucilage.
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Wu X, Huang J, Wang J, Xu Y, Yang X, Sun M, Shi J. Multi-Pharmaceutical Activities of Chinese Herbal Polysaccharides in the Treatment of Pulmonary Fibrosis: Concept and Future Prospects. Front Pharmacol 2021; 12:707491. [PMID: 34489700 PMCID: PMC8418122 DOI: 10.3389/fphar.2021.707491] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 08/04/2021] [Indexed: 12/17/2022] Open
Abstract
Pulmonary fibrosis is a fatal chronic progressive respiratory disease, characterized by continuous scarring of the lung parenchyma, leading to respiratory failure and death. The incidence of PF has increased over time. There are drugs, yet, there are some limitations. Hence, it is of importance to find new therapies and new drugs to replace the treatment of pulmonary fibrosis. In recent years, there have been a great number of research reports on the treatment of traditional Chinese medicine polysaccharides in various system fields. Among them, the treatment of PF has also gained extensive attention. This review summarized the source of polysaccharides, the drug activity of traditional Chinese medicine, and the protective effects on targets of Pulmonary fibrosis. We hope it can inspire researchers to design and develop polysaccharides, serving as a reference for potential clinical therapeutic drugs.
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Affiliation(s)
- Xianbo Wu
- School of Sports Medicine and Health, Chegdu Sport University, Chengdu, China
| | - Jianli Huang
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jie Wang
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Yihua Xu
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xinwei Yang
- School of Sports Medicine and Health, Chegdu Sport University, Chengdu, China
| | - Minghan Sun
- Central of Reproductive Medicine, Department of Obstetrics and Gynecology, School of Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Jianyou Shi
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu, China
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18
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Shahrajabian MH, Sun W, Cheng Q. Chemical components and pharmacological benefits of Basil (Ocimum basilicum): a review. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2020. [DOI: 10.1080/10942912.2020.1828456] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
| | - Wenli Sun
- Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Qi Cheng
- College of Life Sciences, Hebei Agricultural University, Baoding, Hebei, China; Global Alliance of HeBAU-CLS&HeQiS for BioAl-Manufacturing, Baoding, Hebei, China
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19
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He S, Tang S. WNT/β-catenin signaling in the development of liver cancers. Biomed Pharmacother 2020; 132:110851. [PMID: 33080466 DOI: 10.1016/j.biopha.2020.110851] [Citation(s) in RCA: 222] [Impact Index Per Article: 44.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/27/2020] [Accepted: 10/04/2020] [Indexed: 02/06/2023] Open
Abstract
The WNT/β-catenin signaling pathway is a highly conserved and tightly controlled molecular mechanism that regulates embryonic development, cellular proliferation and differentiation. Of note, accumulating evidence has shown that the aberrant of WNT/β-catenin signaling promotes the development and/or progression of liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the two most prevalent primary liver tumours in adults. There are two different WNT signaling pathways have been identified, which were termed non-canonical and canonical pathways, the latter involving the activation of β-catenin. β-catenin, acting as an intracellular signal transducer in the WNT signaling pathway, is encoded by CTNNB1 and plays a critical role in tumorigenesis. In the past research, most liver tumors have mutations in genes encoding key components of the WNT/β-catenin signaling pathway. In addition, several of other signaling pathways also can crosswalk with β-catenin. In this review, we discuss the most relevant molecular mechanisms of action and regulation of WNT/β-catenin signaling in the development and pathophysiology of liver cancers, as well as in the development of therapeutics.
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Affiliation(s)
- Shuai He
- Department of General Surgery, the Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China
| | - Shilei Tang
- Department of General Surgery, the Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China.
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20
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Lim WC, Choi JW, Song NE, Cho CW, Rhee YK, Hong HD. Polysaccharide isolated from persimmon leaves (Diospyros kaki Thunb.) suppresses TGF-β1-induced epithelial-to-mesenchymal transition in A549 cells. Int J Biol Macromol 2020; 164:3835-3845. [PMID: 32835798 DOI: 10.1016/j.ijbiomac.2020.08.155] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 08/12/2020] [Accepted: 08/19/2020] [Indexed: 02/07/2023]
Abstract
In the present study, to verify the effect of polysaccharides derived from persimmon leaves (PLE) at epithelial-to-mesenchymal transition (EMT), A549 cells were treated with TGF-β1 alone or co-treated with TGF-β1 and PLE (50 and 75 μg/mL). PLE-treated cells showed higher expression of E-cadherin and lower expression of N-cadherin and vimentin compared to TGF-β1-treated cells by inhibiting the levels of transcription factors, including Snail, Slug, and ZEB1, all associated with EMT. PLE also significantly decreased migration, invasion, and anoikis resistance through TGF-β1 mediated EMT suppression, whereby PLE inhibited the levels of MMP-2 and MMP-9 while cleaving PARP. These inhibitory effects of PLE against EMT, migration, invasion, and anoikis resistance were determined by activating the canonical SMAD2/3 and non-canonical ERK/p38 signaling pathways. Therefore, these results suggest that PLE could be used as a potential chemical therapeutic agent for early metastasis of lung cancer in vitro.
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Affiliation(s)
- Won-Chul Lim
- Research Group of Traditional Food, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Jae Woong Choi
- Research Group of Traditional Food, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Nho-Eul Song
- Research Group of Traditional Food, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Chang-Won Cho
- Research Group of Traditional Food, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Young Kyoung Rhee
- Research Group of Traditional Food, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Hee-Do Hong
- Research Group of Traditional Food, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea.
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21
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Chu G, Miao Y, Huang K, Song H, Liu L. Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma. Front Bioeng Biotechnol 2020; 8:509. [PMID: 32582655 PMCID: PMC7296140 DOI: 10.3389/fbioe.2020.00509] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 04/30/2020] [Indexed: 12/16/2022] Open
Abstract
Objective: This work is to study the effect of Rhizopus nigrum polysaccharide EPS1-1 on hepatocellular carcinoma (HCC) in vitro and in vivo. Methods: HepG2 and Huh-7 cells and nude mice models of liver cancers were used in this study. The cells and nude mice were treated with EPS1-1 at different concentrations. The CCK8 assays were used to measure the proliferation activities of cells, apoptosis was determined with flow cytometry, cell migration was measured by wound-healing assays, cell invasion was evaluated by Transwell assay, and the survival periods of different groups of tumor-bearing mice were compared. Real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins of the genes related to proliferation, apoptosis, migration, and invasion. Results: In vitro experiments revealed that when treated with EPS1-1, HepG2 and Huh-7 cell proliferation activities decreased, while there was an increase for the apoptosis rate, and the migration and invasion capabilities were significantly reduced. In vivo experiments showed that EPS1-1 could significantly reduce the tumor growth and lung metastasis of HCC, and prolong the survival periods of tumor-bearing nude mice. Furthermore, EPS1-1 has no apparent damage to the heart, liver, and kidney. Further studies showed that EPS1-1 could affect the expression of proliferation-related genes CCND1 and c-Myc, apoptosis-related genes BAX and Bcl-2, and migration and invasion related genes Vimentin and Slug, thereby affecting the biological process of HCC. Conclusion: EPS1-1 can inhibit the malignant process of HCC in vitro and in vivo, which indicates that EPS1-1 has the potential value of clinical application as chemotherapy or adjuvant in the treatment of liver cancer.
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Affiliation(s)
- Guangyu Chu
- Department of Radiology, The Second Hospital of Jilin University, Changchun, China
| | - Yingying Miao
- Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Kexin Huang
- Department of Histology and Embryology, College of Basic Medicine, Jilin University, Changchun, China
| | - Han Song
- Department of Radiology, The Second Hospital of Jilin University, Changchun, China
| | - Liang Liu
- Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, China
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Mossenta M, Busato D, Dal Bo M, Toffoli G. Glucose Metabolism and Oxidative Stress in Hepatocellular Carcinoma: Role and Possible Implications in Novel Therapeutic Strategies. Cancers (Basel) 2020; 12:E1668. [PMID: 32585931 PMCID: PMC7352479 DOI: 10.3390/cancers12061668] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 06/12/2020] [Accepted: 06/20/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) metabolism is redirected to glycolysis to enhance the production of metabolic compounds employed by cancer cells to produce proteins, lipids, and nucleotides in order to maintain a high proliferative rate. This mechanism drives towards uncontrolled growth and causes a further increase in reactive oxygen species (ROS), which could lead to cell death. HCC overcomes the problem generated by ROS increase by increasing the antioxidant machinery, in which key mechanisms involve glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible transcription factor (HIF-1α). These mechanisms could represent optimal targets for innovative therapies. The tumor microenvironment (TME) exerts a key role in HCC pathogenesis and progression. Various metabolic machineries modulate the activity of immune cells in the TME. The deregulated metabolic activity of tumor cells could impair antitumor response. Lactic acid-lactate, derived from the anaerobic glycolytic rate of tumor cells, as well as adenosine, derived from the catabolism of ATP, have an immunosuppressive activity. Metabolic reprogramming of the TME via targeted therapies could enhance the treatment efficacy of anti-cancer immunotherapy. This review describes the metabolic pathways mainly involved in the HCC pathogenesis and progression. The potential targets for HCC treatment involved in these pathways are also discussed.
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Affiliation(s)
- Monica Mossenta
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano (PN), Italy; (M.M.); (D.B.); (G.T.)
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
| | - Davide Busato
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano (PN), Italy; (M.M.); (D.B.); (G.T.)
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
| | - Michele Dal Bo
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano (PN), Italy; (M.M.); (D.B.); (G.T.)
| | - Giuseppe Toffoli
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano (PN), Italy; (M.M.); (D.B.); (G.T.)
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