title: Epigallocatechin-3-gallate potentiates the effect of curcumin in inducing growth inhibition and apoptosis of resistant breast cancer cells.
abstract: Drug resistance remains an on-going challenge in breast cancer chemotherapy. Combination of two or more drugs is an effective strategy to access context-specific multiple targets and overcome undesirable toxicity that is almost inevitable in single-drug chemotherapy. Many plant food-derived polyphenolic compounds have been proven to modulate many key factors responsible for cancer drug resistance, which makes them a promising group of low toxicity candidates for reversing cancer resistance. In this study, we analyzed the combination effect of two chemopreventive polyphenols, curcumin (Cur) and epigallocatechin-3-gallate (EGCG), in combating resistant breast cancer. Our present results showed that EGCG significantly enhanced the growth inhibition and apoptosis in both doxorubicin (DOX)-sensitive and resistant MCF-7 cells induced by Cur. The mechanism may be related to the further activation of caspase-dependent apoptotic signaling pathways and the enhanced cellular incorporation of Cur by inhibiting P-glycoprotein (P-gp) pump function. Moreover, Cur and EGCG in combination could enhance the toxicity of DOX and increase the intracellular level of DOX in resistant MCF-7 cells. Our findings with this practical combination of Cur and EGCG encourage us to move on to a promising strategy for successful treatment of human breast cancer resistance by combining two low-toxic chemotherapeutic agents from diet.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Wang
authors.forename: Ruie
authors.initials: R
authors.lastname: Chen
authors.forename: Zhangfeng
authors.initials: Z
authors.lastname: Zhong
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shi
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000502:physiology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008517:Phytotherapy; D059808:Polyphenols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D059808:Polyphenols; D004317:Doxorubicin; D002392:Catechin; C045651:epigallocatechin gallate; D020169:Caspases; D003474:Curcumin
keywords: Apoptosis; Breast Cancer; Curcumin; Epigallocatechin-3-gallate; Resistance