title: O-Alkylated derivatives of quercetin induce apoptosis of MCF-7 cells via a caspase-independent mitochondrial pathway.
abstract: The aim of this study was to investigate the antitumor effects of two novel alkylated derivatives of quercetin, 7-O-butylquercetin (BQ) and 7-O-geranylquercetin (GQ), in MCF-7 human breast cancer cells and explore the possible cellular mechanism of the related apoptotic effects. Our data showed that BQ and GQ were more toxic to MCF-7 cells and had better accumulation ability in MCF-7 cells than quercetin. Morphological observations and DNA fragmentation pattern suggested that the derivatives could induce apoptosis in MCF-7 cells. Derivatives-induced apoptosis could not be reversed by Z-VAD-FMK and N-acetyl cysteine demonstrated that the apoptosis was independent on caspase and reactive oxygen species. Western blot assay showed that endonuclease G and apoptosis inducing factor might be relative to the apoptosis. Alkylation of quercetin at 7-O position can enhance the apoptosis inducing effect and cell accumulation ability relative to quercetin. This structural alteration brings changes on apoptosis pathway as well.
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liao
authors.affiliation: Clinical Medicine of Seven-year-program, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Bao
authors.affiliation: Second Affiliated Hospital of Dalian Medical University, No.467 Zhongshan Road, Shahekou District, 116027 Dalian, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Qu
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Enxia
authors.initials: E
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Dalian Medical University, No.9 Lvshun Southern Road, Lvshunkou District, 116044 Dalian, China. Electronic address: zhenyhwaner@aliyun.com.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C000607200:7-O-butylquercetin; C000607199:7-O-geranylquercetin; C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D017382:Reactive Oxygen Species; D011794:Quercetin; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases
keywords: Alkylated quercetin derivatives; Apoptosis; Apoptosis inducing factor; Breast cancer; Endonuclease G