title: Genistein induces activation of the mitochondrial apoptosis pathway by inhibiting phosphorylation of Akt in colorectal cancer cells.
abstract: BACKGROUND
  Genistein inhibits the proliferation and induces apoptosis of colorectal cancer cells; however, the underling molecular mechanisms remain to be determined.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether genistein reduces cell viability by suppressing the phosphorylation of AKT and activating the mitochondrial apoptosis pathway in colorectal cancer cells.
  
  
  METHODS
  The anti-proliferative effects of genistein (0, 25, 50, and 100 μM) on HCT-116 and LoVo cells were assessed using MTT assay. Genistein-induced apoptosis was measured by Hoechst 33258 staining and flow cytometry. The mRNA level of Bax was detected by real-time PCR. The protein levels of Bax, total Akt, and phosphorylated Akt were assessed by western blot.
  
  
  RESULTS
  The IC50 values of genistein were 690, 135, and 61 μM in HCT-116 cells and 204, 135, and 93 μM in LoVo cells after treatment for 24, 48, and 72 h, respectively. After treatment with different concentrations of genistein (0, 25, 50, and 100 μM) for 48 h, the early apoptotic cells in HCT-116 increased from 1.99% ± 0.55% to 6.78% ± 2.12%, 23.16% ± 3.87%, and 36.99% ± 3.76%, respectively. The same concentrations of genistein increased the early apoptotic cells in LoVo from 2.56% ± 1.42% to 3.21% ± 1.52%, 18.22% ± 3.56%, and 23.56% ± 3.02%, respectively. Moreover, genistein increased the mRNA and protein levels of Bax, while it inhibited the phosphorylation of Akt in HCT-116 cells.
  
  
  CONCLUSIONS
  Genistein inhibited cell proliferation and induced apoptosis of colorectal cancer cells. Genistein induced the mitochondrial pathway of apoptosis in HCT-116 cells by inhibiting phosphorylation of Akt.
authors.affiliation: a Department of Radiation Oncology of Clinical Cancer Center .
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
authors.affiliation: b Department of Cadre Medicine , Division of Endocrinology and Metabolism and.
authors.forename: JiaAn
authors.initials: J
authors.lastname: Teng
authors.affiliation: c Department of Gastrointestinal and Peripheral Vascular Surgery , the People's Hospital of Guangxi Zhuang Autonomous Region , Nanning , China , and.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: a Department of Radiation Oncology of Clinical Cancer Center .
authors.forename: JiaXin
authors.initials: J
authors.lastname: Chen
authors.affiliation: d Department of Physiology , Guilin Medical University , Guilin , China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; D019833:Genistein; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; HCT-116; LoVo; apoptosis; bax; colorectal cancer cell; genistein