TY - JOUR AB - Colorectal cancer (CRC) is a worldwide malignancy of high incidence and mortality. At present, there is a lack of effective drugs against CRC. The B‑cell leukemia/lymphoma 2 (Bcl‑2) protein family members are considered to be closely associated with tumorigenesis and the chemoresistance of CRC. As a novel gossypol derivative targeting antiapoptotic proteins of the Bcl‑2 family, apogossypolone (ApoG2) exhibits antitumor properties in various cancer types, although its effects against CRC remain to be fully elucidated. In the present study, the cytotoxicity of ApoG2 in vitro on CRC cells was investigated, with the aim of elucidating the underlying mechanism. Using an MTT assay, ApoG2 was revealed to inhibit the growth of the HT29, SW480 and HCT116 CRC cell lines in a dose‑ and a time‑dependent manner. Hoechst staining revealed that ApoG2 induced CRC cell apoptosis, marked by morphological changes, including cell shrinkage and nuclear fragmentation. Flow cytometric analysis also detected a higher apoptotic ratio following treatment with ApoG2. The ratio was dependent upon the concentration of ApoG2, which the cells were exposed to, and the duration of the exposure. Western blot analysis and immunoprecipitation experiments revealed that ApoG2 treatment led to the downregulation of the protein expression of Mcl‑1, and the interruption of the binding of Mcl‑1 to the protein Bax. Furthermore, treatment with ApoG2 led to the release of cytochrome c into the cytoplasm and the activation of caspases 3 and 7. The present study revealed that ApoG2 inhibited the proliferation of the CRC cell lines through mitochondrial signaling pathway‑dependent apoptosis, which may be associated with the disruption of the function of the Mcl‑1 protein by ApoG2. AD - Department of Clinical Research, Sun Yat‑sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China Department of Geriatrics, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China Department of Neurology, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China AU - Li,Tianxiao AU - Yuan,Gang AU - Zhang,Lin AU - Ye,Lijun AU - Li,Shuxia AU - Fan,Yuhua AU - Sun,Jian DA - 2015/11/01 DO - 10.3892/mmr.2015.4299 EP - 6984 IS - 5 JO - Mol Med Rep KW - apogossypolone B‑cell leukemia/lymphoma 2 family colorectal cancer PY - 2015 SN - 1791-2997 1791-3004 SP - 6976 ST - ApoG2 inhibits the antiapoptotic protein, Mcl‑1, and induces mitochondria‑dependent apoptosis in human colorectal cancer cells T2 - Molecular Medicine Reports TI - ApoG2 inhibits the antiapoptotic protein, Mcl‑1, and induces mitochondria‑dependent apoptosis in human colorectal cancer cells UR - https://doi.org/10.3892/mmr.2015.4299 VL - 12 ER -