EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer.
Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1), a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP). The present study demonstrates for the first time that (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Beijing Research Institute for Nutritional Resources, Beijing, China.
Xuemin
X
Wang
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Pan
P
Jiang
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Pengqi
P
Wang
Department of Chemical Biology, Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey, United States of America.
Chung S
CS
Yang
Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu, China.
Xuerong
X
Wang
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Qing
Q
Feng
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D000079923:Copper Transporter 1; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; C490077:Slc31a1 protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate; D002945:Cisplatin