title: Neohesperidin induces cellular apoptosis in human breast adenocarcinoma MDA-MB-231 cells via activating the Bcl-2/Bax-mediated signaling pathway.
abstract: Neohesperidin, a flavonoid compound found in high amounts in Poncirus trifoliata, has free radical scavenging activity. For the first time, our study indicated that neohesperidin also induces cell apoptosis in human breast adenocarcinoma MDA-MB-231 cells, which was possibly mediated by regulating the P53/Bcl-2/Bax pathway. MDA-MB-231 cells were subjected to treatment with neohesperidin. MTT and Trypan blue exclusion assays were applied to assess the cell viability. The morphological changes of cells were observed using an inverted microscope, and cell apoptosis was detected by flow cytometric analysis. Immunoblot analysis was conducted to evaluate the protein expressions of apoptosis-related genes, including P53, Bcl-2 and Bax. Our results indicated that the proliferation of MDA-MB-231 cells was inhibited by the treatment with neohesperidin in a time- and dose-dependent manner. The IC50 values of neohesperidin at 24 and 48 h were 47.4 +/- 2.6 microM and 32.5 +/- 1.8 microM, respectively. The expressions of P53 and Bax in the neohesperidin-treated cells were significantly up-regulated, while that of Bcl-2 was down-regulated. Our study suggested that neohesperidin could induce apoptosis of MDA-MB-231 cells, a process which was associated with the activation of the Bcl-2/Bax-mediated signaling pathway.
authors.affiliation: Department of Laboratory Medicine, Wuxi Municipal Women and Children Health Hospital, Wuxi 214002, Jiangsu Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Zang
authors.forename: Daozhen
authors.initials: D
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhan
authors.forename: Mudan
authors.initials: M
authors.lastname: Lu
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Zhuge
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; D006569:Hesperidin; C546526:neohesperidin