Induction of Bax and activation of caspases during beta-sitosterol-mediated apoptosis in human colon cancer cells.
beta-sitosterol, a main dietary phytosterol found in plants, may have the potential for prevention and therapy for human cancer. The purpose of the present study was to examine the effect of beta-sitosterol on the growth of HT116 human colon cancer cells. Treatment with beta-sitosterol resulted in a dose-dependent growth inhibition coupled with the characteristic morphological features of apoptosis and with the increase of a sub-G1 cell population. Apoptosis-inducing concentrations of beta-sitosterol induced caspase-3 and caspase-9 activation accompanied by proteolytic cleavage of poly(ADP-ribose)-polymerase. In addition, beta-sitosterol-induced apoptosis in HT116 cells was associated with a decreased expression of the anti-apototic Bcl-2 protein and mRNA and a concomitant increase of the pro-apototic Bax protein and mRNA, and with release of cytochrome c from the mitochondria into the cytosol. beta-sitosterol treatment also inhibited the expression of cIAP-1 without significant changes in the level of cIAP-2. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of beta-sitosterol.
Choi
Yung Hyun
YH
Department of Biochemistry, Dong-Eui University College of Oriental Medicine, Busan 614-052, Korea. choiyh@dongeui.ac.kr
Kong
Kyu Ri
KR
Kim
Young-Ae
YA
Jung
Keun-Ok
KO
Kil
Jeong-Ha
JH
Rhee
Sook-Hee
SH
Park
Kun-Young
KY
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012855:Sitosterols / Q000378:metabolism / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D000960:Hypolipidemic Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012855:Sitosterols; D051028:bcl-2-Associated X Protein; C025473:gamma-sitosterol; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases