EGCG抗肿瘤作用及其相关靶点的研究进展
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摘要
表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)是绿茶的主要生物活性成分,是一种多酚类物质,属于茶多酚的一种。多年来研究发现其在抗氧化、抗炎、抗心血管疾病、抗肥胖、抗糖尿病、抗神经系统疾病、抗肿瘤等等方面发挥了预防及潜在的治疗作用,并可与多种蛋白靶点作用,影响多种化学通路发挥其上述生物学作用,如跟自噬相关蛋白LC3-Ⅰ直接结合促进LC3-Ⅱ的形成进而促进自噬,作用于PI3K/AKT通路影响细胞自噬、细胞凋亡、血管生成和细胞周期调控等等。现对其在抗肿瘤方面的作用及其相关靶点作一综述。
Epigallocatechin gallate( EGCG) is the main bioactive component of green tea and is a polyphenolic substance that belongs to the class of tea polyphenols. Over the years,it has been discovered that it has played a preventive and potential therapeutic role in anti-oxidation,anti-inflammatory,anti-cardiovascular diseases,anti-obesity,anti-diabetic,anti-neurological diseases,anti-tumor,and so on. It can interact with multiple protein targets and affect various biological pathways to exert its biological effects. For example,direct binding to autophagy-related protein LC3-Ⅰ promotes the formation of LC3-Ⅱ and promotes autophagy,acting on the PI3K/AKT pathway to affect cell autophagy,apoptosis,angiogenesis,and cell cycle regulation. Its anti-tumor role and its related targets are reviewed.
Epigallocatechin gallate( EGCG) is the main bioactive component of green tea and is a polyphenolic substance that belongs to the class of tea polyphenols. Over the years,it has been discovered that it has played a preventive and potential therapeutic role in anti-oxidation,anti-inflammatory,anti-cardiovascular diseases,anti-obesity,anti-diabetic,anti-neurological diseases,anti-tumor,and so on. It can interact with multiple protein targets and affect various biological pathways to exert its biological effects. For example,direct binding to autophagy-related protein LC3-Ⅰ promotes the formation of LC3-Ⅱ and promotes autophagy,acting on the PI3K/AKT pathway to affect cell autophagy,apoptosis,angiogenesis,and cell cycle regulation. Its anti-tumor role and its related targets are reviewed.
引文
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[2]Li W,Zhu S,Li J,et al. EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages[J]. Biochemical Pharmacology,2011,81(9):1152-1163.
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[7]Wang W,Chen D,Zhu K. SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition[J]. Journal of Experimental&Clinical Cancer Research,2018,37(1):37.
[8]Li S,Xia Y,Chen K,et al. Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3[J]. Drug Design Development&Therapy,2016,10(1):631-647.
[9]Chen Y,Huang L,Zhang H,et al. Reduction in autophagy by(-)-epigallocatechin-3-gallate(EGCG):A potential mechanism of prevention of mitochondrial dysfunction after subarachnoid hemorrhage[J]. Molecular Neurobiology,2017,54(1):392-405.
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[12]Yang C,Du W,Yang D. Inhibition of green tea polyphenol EGCG[(-)-epigallocatechin-3-gallate]on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway[J]. International Journal of Food Sciences&Nutrition,2016,67(7):818-827.
[13]Valenti D,De BL,Manente GA,et al. Negative modulation of mitochondrial oxidative phosphorylation by epigallocatechin-3 gallate leads to growth arrest and apoptosis in human malignant pleural mesothelioma cells[J]. Biochim Biophys Acta,2013,1832(12):2085-2096.
[14]Mayr C,Wagner A,Neureiter D,et al. The green tea catechin epigallocatechin gallate induces cell cycle arrest and shows potential synergism with cisplatin in biliary tract cancer cells[J]. Bmc Complementary&Alternative Medicine,2015,15(1):1-7.
[15]Tang P,Sun Q,Yang H,et al. Honokiol nanoparticles based on epigallocatechin gallate functionalized chitin to enhance therapeutic effects against liver cancer[J]. Int J Pharm,2018,45(1-2):74-83.
[16]Liu S,Xu ZL,Sun L,et al. Epigallocatechin-3-gallate induces apoptosis in human pancreatic cancer cells via PTEN[J]. Molecular Medicine Reports,2016,14(1):599-605.
[17]Meng J,Tong Q,Liu X,et al. Epigallocatechin-3-gallate inhibits growth and induces apoptosis in esophageal cancer cells through the demethylation and reactivation of the p16 gene[J].Oncology Letters,2017,14(1):1152.
[18]Liu L,Zuo J,Wang G. Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis in Ec9706 and Eca109esophageal carcinoma cells[J]. Oncology Letters,2017,14(4):4391.
[19]Liu L,Ju Y,Wang J,et al. Epigallocatechin-3-gallate promotes apoptosis and reversal of multidrug resistance in esophageal cancer cells[J]. Pathol Res Pract,2017,213(10):1242-1250.
[20]Feng C,Ho Y,Sun C,et al. Epigallocatechin gallate inhibits the growth and promotes the apoptosis of bladder cancer cells[J]. Experimental&Therapeutic Medicine,2017,14(4):3513.
[21]Wang J,Zhu C,Song D,et al. Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity[J]. Cell Death Discovery,2017,3:17034.
[22]Moradzadeh M,Hosseini A,Erfanian S,et al. Epigallocatechin-3-gallate promotes apoptosis in human breast cancer T47D cells through down-regulation of PI3K/AKT and Telomerase[J].Pharmacological Reports,2017,69(5):924-928.
[23]Huang CY,Han Z,Li X,et al. Mechanism of EGCG promoting apoptosis of MCF-7 cell line in human breast cancer[J]. Oncology Letters,2017,14(3):3623-3627.
[24]Zhou CG,Hui LM,Luo JM,et al. Epigallocatechin gallate inhibits the proliferation and induces apoptosis of multiple myeloma cells via inactivating EZH2[J]. Eur Rev Med Pharmacol Sci,2018,22(7):2093-2098.
[25]Kantono M,Guo B. Inflammasomes and cancer:The dynamic role of the inflammasome in tumor development[J]. Frontiers in Immunology,2017,8:1132.
[26]Xie H,Sun J,Chen Y,et al. EGCG attenuates uric acid-induced inflammatory and oxidative stress responses by medicating the NOTCH pathway[J]. Oxidative Medicine and Cellular Longevity,2015,2015(1):1-10.
[27]Liu D,Perkins JT,Hennig B. EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells[J]. Journal of Nutritional Biochemistry,2016,28:164.
[28]Liu W,Dong M,Bo L,et al. Epigallocatechin-3-gallate ameliorates seawater aspiration-induced acute lung injury via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats[J]. Mediators Inflamm,2015,2014(7):612593.
[29]Mukherjee S,Siddiqui MA,Dayal S,et al. Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells[J]. Journal of Inflammation Research,2014,7:89-101.
[30]Rashidi B,Malekzadeh M,Goodarzi M,et al. Green tea and its anti-angiogenesis effects[J]. Biomedicine&Pharmacotherapy,2017,89:949-956.
[31]Jin G,Yang Y,Liu K,et al. Combination curcumin and(-)-epigallocatechin-3-gallate inhibits colorectal carcinoma microenvironment-induced angiogenesis by JAK/STAT3/IL-8 pathway[J]. Oncogenesis,2017,6(10):e384.
[32]Shi J,Liu F,Zhang W,et al. Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by the suppression of angiogenesis and epithelial-mesenchymal transition in nonsmall cell lung cancer cells[J]. Oncology Reports,2015,33(6):2972.
[33]Wang J,Man G,Chan TH,et al. A prodrug of green tea polyphenol(-)-epigallocatechin-3-gallate(Pro-EGCG)serves as a novel angiogenesis inhibitor in endometrial cancer[J]. Cancer Letters,2018,412:10-20.
[34]Sakamoto Y,Terashita N,Muraguchi T,et al. Effects of epigallocatechin-3-gallate(EGCG)on A549 lung cancer tumor growth and angiogenesis[J]. Journal of the Agricultural Chemical Society of Japan,2013,77(9):1799-1803.
[35]Hashimoto O,Nakamura A,Nakamura T,et al. Methylated-(3')-epigallocatechin gallate analog suppresses tumor growth in Huh7 hepatoma cells via inhibition of angiogenesis[J]. Nutrition&Cancer,2014,66(4):728-735.
[36]Luo KW,Chen W,Lung WY,et al. EGCG inhibited bladder cancer SW780 cell proliferation and migration both in vitro and in vivo via down-regulation of NF-κB and MMP-9[J]. Journal of Nutritional Biochemistry,2017,41:56-64.
[37]Zhou F,Zhou H,Wang T,et al. Epigallocatechin-3-gallate inhibits proliferation and migration of human colon cancer SW620cells in vitro[J]. Acta Pharmacol Sin,2012,3(1):120-126.
[38]Farabegoli F,Govoni M,Spisni E,et al. EGFR inhibition by(-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion[J]. Bioscience Reports,2017,37(3):BSR20170168.
[39]Li YJ,Wu SL,Lu SM,et al.(-)-Epigallocatechin-3-gallate inhibits nasopharyngeal cancer stem cell self-renewal and migration and reverses the epithelial-mesenchymal transition via NF-κB p65 inactivation[J]. Tumour Biology,2015,36(4):2747.
[2]Li W,Zhu S,Li J,et al. EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages[J]. Biochemical Pharmacology,2011,81(9):1152-1163.
[3]Huang CY,Chiang SF,Ke TW,et al. Cytosolic high-mobility group box protein 1(HMGB1)and/or PD-1+TILs in the tumor microenvironment may be contributing prognostic biomarkers for patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy[J]. Cancer Immunology Immunotherapy,2018,67(4):551-562.
[4]Xiao Y,Sun L,Fu Y,et al. High mobility group box 1 promotes sorafenib resistance in Hep G2cells and in vivo[J]. Bmc Cancer,2017,17(1):857.
[5]Tsai CY,Chen CY,Chiou YH,et al. Epigallocatechin-3-gallate suppresses human herpesvirus 8 replication and induces ROS leading to apoptosis and autophagy in primary effusion lymphoma cells[J]. International Journal of Molecular Sciences,2017,19(1):16.
[6]Holczer M,Besze B,ZámbóV,et al. Epigallocatechin-3-gallate(EGCG)promotes autophagy-dependent survival via influencing the balance of m TOR-AMPK pathways upon endoplasmic reticulum stress[J]. Oxidative Medicine&Cellular Longevity,2018,2018:6721530.
[7]Wang W,Chen D,Zhu K. SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition[J]. Journal of Experimental&Clinical Cancer Research,2018,37(1):37.
[8]Li S,Xia Y,Chen K,et al. Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3[J]. Drug Design Development&Therapy,2016,10(1):631-647.
[9]Chen Y,Huang L,Zhang H,et al. Reduction in autophagy by(-)-epigallocatechin-3-gallate(EGCG):A potential mechanism of prevention of mitochondrial dysfunction after subarachnoid hemorrhage[J]. Molecular Neurobiology,2017,54(1):392-405.
[10]Huang J,Chen S,Shi Y,et al. Epigallocatechin gallate from green tea exhibits potent anticancer effects in A-549 non-small lung cancer cells by inducing apoptosis,cell cycle arrest and inhibition of cell migration[J]. Journal of Buon,2017,22(6):1422-1427.
[11]Chakrabarty S,Ganguli A,Das A,et al. Epigallocatechin-3-gallate shows anti-proliferative activity in He La cells targeting tubulin-microtubule equilibrium[J]. Chemico-Biological Interactions,2015,242:380-389.
[12]Yang C,Du W,Yang D. Inhibition of green tea polyphenol EGCG[(-)-epigallocatechin-3-gallate]on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway[J]. International Journal of Food Sciences&Nutrition,2016,67(7):818-827.
[13]Valenti D,De BL,Manente GA,et al. Negative modulation of mitochondrial oxidative phosphorylation by epigallocatechin-3 gallate leads to growth arrest and apoptosis in human malignant pleural mesothelioma cells[J]. Biochim Biophys Acta,2013,1832(12):2085-2096.
[14]Mayr C,Wagner A,Neureiter D,et al. The green tea catechin epigallocatechin gallate induces cell cycle arrest and shows potential synergism with cisplatin in biliary tract cancer cells[J]. Bmc Complementary&Alternative Medicine,2015,15(1):1-7.
[15]Tang P,Sun Q,Yang H,et al. Honokiol nanoparticles based on epigallocatechin gallate functionalized chitin to enhance therapeutic effects against liver cancer[J]. Int J Pharm,2018,45(1-2):74-83.
[16]Liu S,Xu ZL,Sun L,et al. Epigallocatechin-3-gallate induces apoptosis in human pancreatic cancer cells via PTEN[J]. Molecular Medicine Reports,2016,14(1):599-605.
[17]Meng J,Tong Q,Liu X,et al. Epigallocatechin-3-gallate inhibits growth and induces apoptosis in esophageal cancer cells through the demethylation and reactivation of the p16 gene[J].Oncology Letters,2017,14(1):1152.
[18]Liu L,Zuo J,Wang G. Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis in Ec9706 and Eca109esophageal carcinoma cells[J]. Oncology Letters,2017,14(4):4391.
[19]Liu L,Ju Y,Wang J,et al. Epigallocatechin-3-gallate promotes apoptosis and reversal of multidrug resistance in esophageal cancer cells[J]. Pathol Res Pract,2017,213(10):1242-1250.
[20]Feng C,Ho Y,Sun C,et al. Epigallocatechin gallate inhibits the growth and promotes the apoptosis of bladder cancer cells[J]. Experimental&Therapeutic Medicine,2017,14(4):3513.
[21]Wang J,Zhu C,Song D,et al. Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity[J]. Cell Death Discovery,2017,3:17034.
[22]Moradzadeh M,Hosseini A,Erfanian S,et al. Epigallocatechin-3-gallate promotes apoptosis in human breast cancer T47D cells through down-regulation of PI3K/AKT and Telomerase[J].Pharmacological Reports,2017,69(5):924-928.
[23]Huang CY,Han Z,Li X,et al. Mechanism of EGCG promoting apoptosis of MCF-7 cell line in human breast cancer[J]. Oncology Letters,2017,14(3):3623-3627.
[24]Zhou CG,Hui LM,Luo JM,et al. Epigallocatechin gallate inhibits the proliferation and induces apoptosis of multiple myeloma cells via inactivating EZH2[J]. Eur Rev Med Pharmacol Sci,2018,22(7):2093-2098.
[25]Kantono M,Guo B. Inflammasomes and cancer:The dynamic role of the inflammasome in tumor development[J]. Frontiers in Immunology,2017,8:1132.
[26]Xie H,Sun J,Chen Y,et al. EGCG attenuates uric acid-induced inflammatory and oxidative stress responses by medicating the NOTCH pathway[J]. Oxidative Medicine and Cellular Longevity,2015,2015(1):1-10.
[27]Liu D,Perkins JT,Hennig B. EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells[J]. Journal of Nutritional Biochemistry,2016,28:164.
[28]Liu W,Dong M,Bo L,et al. Epigallocatechin-3-gallate ameliorates seawater aspiration-induced acute lung injury via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats[J]. Mediators Inflamm,2015,2014(7):612593.
[29]Mukherjee S,Siddiqui MA,Dayal S,et al. Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells[J]. Journal of Inflammation Research,2014,7:89-101.
[30]Rashidi B,Malekzadeh M,Goodarzi M,et al. Green tea and its anti-angiogenesis effects[J]. Biomedicine&Pharmacotherapy,2017,89:949-956.
[31]Jin G,Yang Y,Liu K,et al. Combination curcumin and(-)-epigallocatechin-3-gallate inhibits colorectal carcinoma microenvironment-induced angiogenesis by JAK/STAT3/IL-8 pathway[J]. Oncogenesis,2017,6(10):e384.
[32]Shi J,Liu F,Zhang W,et al. Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by the suppression of angiogenesis and epithelial-mesenchymal transition in nonsmall cell lung cancer cells[J]. Oncology Reports,2015,33(6):2972.
[33]Wang J,Man G,Chan TH,et al. A prodrug of green tea polyphenol(-)-epigallocatechin-3-gallate(Pro-EGCG)serves as a novel angiogenesis inhibitor in endometrial cancer[J]. Cancer Letters,2018,412:10-20.
[34]Sakamoto Y,Terashita N,Muraguchi T,et al. Effects of epigallocatechin-3-gallate(EGCG)on A549 lung cancer tumor growth and angiogenesis[J]. Journal of the Agricultural Chemical Society of Japan,2013,77(9):1799-1803.
[35]Hashimoto O,Nakamura A,Nakamura T,et al. Methylated-(3')-epigallocatechin gallate analog suppresses tumor growth in Huh7 hepatoma cells via inhibition of angiogenesis[J]. Nutrition&Cancer,2014,66(4):728-735.
[36]Luo KW,Chen W,Lung WY,et al. EGCG inhibited bladder cancer SW780 cell proliferation and migration both in vitro and in vivo via down-regulation of NF-κB and MMP-9[J]. Journal of Nutritional Biochemistry,2017,41:56-64.
[37]Zhou F,Zhou H,Wang T,et al. Epigallocatechin-3-gallate inhibits proliferation and migration of human colon cancer SW620cells in vitro[J]. Acta Pharmacol Sin,2012,3(1):120-126.
[38]Farabegoli F,Govoni M,Spisni E,et al. EGFR inhibition by(-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion[J]. Bioscience Reports,2017,37(3):BSR20170168.
[39]Li YJ,Wu SL,Lu SM,et al.(-)-Epigallocatechin-3-gallate inhibits nasopharyngeal cancer stem cell self-renewal and migration and reverses the epithelial-mesenchymal transition via NF-κB p65 inactivation[J]. Tumour Biology,2015,36(4):2747.