Biological Activity
apogossypolone is an inhibitor of bcl-2, mcl-1 and bcl-xl with ki values of 35nm, 25nm and 660nm, respectively [1].the mtt-based cell cytotoxicity assay shows that apogossypolone has an anticancer activity with ic50 values of 1, 2 and 3μm, respectively in pc-3, du-145 (human prostate cancer cell lines) and mda-mb-231(human breast cancer cell line). apogossypolone is also found to inhibit the colony formation of du-145 cells. the mechanism is that apogossypolone binds to bcl-2 and prevents its association with bh3-only pro-apoptotic proteins, leading the pro-apoptotic proteins to participate in the apoptotic response [2].besides prostate cancer and breast cancer, apogossypolone is also potent in follicular lymphoma. apogossypolone significantly inhibits the cell growth via inducing apoptosis in wsu-fsccl cell line with ic50 value of 109.2nm at 72h [3].
References
[1] zhang xq, huang xf, hu xb, zhan yh, an qx, yang sm, xia aj, yi j, chen r, mu sj, wu dc. apogossypolone, a novel inhibitor of antiapoptotic bcl-2 family proteins, induces autophagy of pc-3 and lncap prostate cancer cells in vitro. asian j androl. 2010 sep;12(5):697-708.
[2] zhan y, jia g, wu d, xu y, xu l. design and synthesis of a gossypol derivative with improved antitumor activities. arch pharm (weinheim). 2009 apr;342(4):223-9.
[3] arnold aa, aboukameel a, chen j, yang d, wang s, al-katib a, mohammad rm. preclinical studies of apogossypolone: a new nonpeptidic pan small-molecule inhibitor of bcl-2, bcl-xl and mcl-1 proteins in follicular small cleaved cell lymphoma model. mol cancer. 2008 feb 14;7:20.
