TY - JOUR
T1 - Molecular mechanism of gossypol-induced cell growth inhibition and cell death of HT-29 human colon carcinoma cells
AU - Zhang, Manchao
AU - Liu, Hongpeng
AU - Guo, Ribo
AU - Ling, Yan
AU - Wu, Xiaojin
AU - Li, Bihua
AU - Roller, Peter P.
AU - Wang, Shaomeng
AU - Yang, Dajun
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Gossypol, a male contraceptive drug, has been demonstrated to have antiproliferative and antimetastatic effects on many kinds of cancer cells in vitro. HT-29 human carcinoma cell line is one of the most susceptible cell lines to gossypol-induced cell death. Here, it is shown that treatment of HT-29 cells with gossypol not only induces cell cycle arrest on the G0/G1 phase, but also induces apoptosis. With a serial of Western blot analysis, it is revealed that gossypol-induced cell cycle arrest is involved in P21 up-regulation and cyclin D1 down-regulation; gossypol-induced apoptosis triggers down-regulation of anti-apoptosis Bcl-2 members: Bcl-XL, Bag-1 and Mcl-1, up-regulation of pro-apoptosis Bcl-2 member Bak, activation of caspase-3, -6, -7, -8, and -9, up-regulation of Apaf-1, release of cytochrome c (cyto-c) from mitochondria, and activation of both DFF45 and PARP. Taken together, gossypol-induced cell death initiates extensive alterations of cell cycle and apoptosis proteins. Gossypol-induced apoptosis of HT-29 cells is through first the mitochondrial pathway, then the death receptor pathway, and the mitochondria pathway is, at least in part, involved in cyto-c release.
AB - Gossypol, a male contraceptive drug, has been demonstrated to have antiproliferative and antimetastatic effects on many kinds of cancer cells in vitro. HT-29 human carcinoma cell line is one of the most susceptible cell lines to gossypol-induced cell death. Here, it is shown that treatment of HT-29 cells with gossypol not only induces cell cycle arrest on the G0/G1 phase, but also induces apoptosis. With a serial of Western blot analysis, it is revealed that gossypol-induced cell cycle arrest is involved in P21 up-regulation and cyclin D1 down-regulation; gossypol-induced apoptosis triggers down-regulation of anti-apoptosis Bcl-2 members: Bcl-XL, Bag-1 and Mcl-1, up-regulation of pro-apoptosis Bcl-2 member Bak, activation of caspase-3, -6, -7, -8, and -9, up-regulation of Apaf-1, release of cytochrome c (cyto-c) from mitochondria, and activation of both DFF45 and PARP. Taken together, gossypol-induced cell death initiates extensive alterations of cell cycle and apoptosis proteins. Gossypol-induced apoptosis of HT-29 cells is through first the mitochondrial pathway, then the death receptor pathway, and the mitochondria pathway is, at least in part, involved in cyto-c release.
KW - Apoptosis
KW - Bcl-X
KW - Caspases
KW - Cell cycle
KW - Cyclin D1
KW - Cytochrome c release
KW - DFF45
KW - HT-29
KW - P21
KW - PARP
UR - http://www.scopus.com/inward/record.url?scp=0038682166&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038682166&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(03)00248-X
DO - 10.1016/S0006-2952(03)00248-X
M3 - Article
C2 - 12818369
AN - SCOPUS:0038682166
SN - 0006-2952
VL - 66
SP - 93
EP - 103
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 1
ER -