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DIFFERENTIAL GROWTH INHIBITION AND INDUCTION OF APOPTOSIS BY GOSSYPOL BETWEEN HCT116 AND HCT116/BAX −/– COLORECTAL CANCER CELLS
Author(s) -
Zhang Manchao,
Liu Hongpeng,
Tian Zhenkun,
Huang Jenny,
Remo Mylene,
Li Q Quentin
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04577.x
Subject(s) - gossypol , apoptosis , programmed cell death , growth inhibition , bcl 2 associated x protein , cell growth , chemistry , microbiology and biotechnology , caspase 3 , cell culture , biology , biochemistry , genetics
SUMMARY1 Bax is a very important pro‐apoptosis molecule. HCT116/Bax −/– cells do not express the pro‐apoptosis Bcl‐2 family member, Bax. In the present study, the anticancer effects of gossypol on HCT116 and HCT116/Bax −/– cells were compared in terms of inhibition of cell growth, inhibition of colony formation and induction of apoptosis. 2 Following treatment with concentrations more than 20 µmol/L gossypol, only slight differences (not signficant) were seen between HCT116 and HCT116/Bax −/– cells in terms of the inhibition of cell growth and induction of apoptosis. No difference was seen in the inhibition of colony formation. Gossypol had no effect at concentrations < 2 µmol/L. The only effective concentration of gossypol to result in differences between HCT116 and HCT116/Bax −/– cells was 5 µmol/L. However, even at this concentration, Bax deficiency did not result in complete abolition of gossypol‐induced growth inhibition or apoptosis. Exposure of cells to 5 µmol/L gossypol for 24 h did not cause any significant difference in the activation of caspase 2 between HCT116 and HCT116/Bax −/– cells; however, activation of caspase 3, 8 and 9 was significantly elevated in HCT116 cells, with the effect on caspase 3 activation being the greatest, compared with HCT116/Bax −/– cells. 3 These findings suggest that the contribution of Bax to gossypol‐induced growth inhibition and apoptosis is dose dependent and that gossypol‐induced apoptosis requires activation of caspase 3, 8, and 9.