title: 3',4',5',5,7-pentamethoxyflavone sensitizes Cisplatin-resistant A549 cells to Cisplatin by inhibition of Nrf2 pathway.
abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important redox-sensitive transcription factor that regulates the expression of several cytoprotective genes. More recently, genetic analyses of human tumors have indicated that Nrf2 may cause resistance to chemotherapy. In this study, we found that the expression levels of Nrf2 and its target genes GCLC, HO-1, NQO1 were significantly higher in cisplatin-resistant A549 (A549/CDDP) cells than those in A549 cells, and this resistance was partially reversed by Nrf2 siRNA. 3',4',5',5,7-Pentamethoxyflavone (PMF), a natural flavonoid extracted from Rutaceae plants, sensitized A549/CDDP to CDDP and substantially induced apoptosis compared with that of CDDP alone treated group, and this reversal effect decreased when Nrf2 was downregulated by siRNA. Mechanistically, PMF reduced Nrf2 expression leading to a reduction of Nrf2 downstream genes, and in contrast, this effect was decreased by blocking Nrf2 with siRNA. Taken together, these results demonstrated that PMF could be used as an effective adjuvant sensitizer to increase the efficacy of chemotherapeutic drugs by downregulating Nrf2 signaling pathway.
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Hou
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xupeng
authors.initials: X
authors.lastname: Bai
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gou
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zeng
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xia
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xinmeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C488726:5,7,3',4',5'-pentamethoxyflavone; D000970:Antineoplastic Agents; D005419:Flavonoids; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D002945:Cisplatin
keywords: 3′,4′,5′,5,7-Pentamethoxyflavone; Nrf2; chemoresistance; cisplatin; lung cancer
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