title: 8‑bromo‑7‑methoxychrysin induces apoptosis by regulating Akt/FOXO3a pathway in cisplatin‑sensitive and resistant ovarian cancer cells.
abstract: 8‑bromo‑7‑methoxychrysin (BrMC), a novel chrysin analog, was reported to have anti‑cancer activities. The aim of the present study was to investigate the molecular mechanism of 8‑bromo‑7‑methoxychrysin (BrMC)‑induced apoptosis via the Akt/forkhead box O3a (FOXO3a) pathway in cisplatin (DDP)‑sensitive and ‑resistant ovarian cancer cells. The human ovarian cancer cell lines A2780 and A2780/DDP were cultured in vitro. Various molecular techniques were used to assess the expression of FOXO3a and B cell lymphoma 2 (Bcl‑2)‑interacting mediator of cell death (Bim) in cisplatin‑sensitive and ‑resistant ovarian cancer cells. Different concentrations of BrMC induced apoptosis in cisplatin‑sensitive and ‑resistant ovarian cancer cells. BrMC‑induced apoptotic cell death occurred mainly by the activation of Akt, which was accompanied by the overexpression of transcription factor FOXO3a, with a concomitant increase in the expression levels of Bim. Silencing Bim expression by using small interfering RNA, attenuated the induction of apoptosis by BrMC treatment. The results indicated that BrMC‑induced apoptosis in cisplatin‑sensitive and ‑resistant ovarian cancer cells may occur via the regulation of Akt/FOXO3a, leading to Bim transcription.
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R.China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R.China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R.China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R.China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R.China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R.China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Dai
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R.China.
authors.forename: Sudan
authors.initials: S
authors.lastname: Cao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C552860:8-bromo-7-methoxychrysin; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C499517:FOXO3 protein, human; D005419:Flavonoids; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin