Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3.
Sulforaphane (SFN) is an isothiocyanate that is found in abundant quantities in many cruciferous vegetables including broccoli and cauliflower. Its inhibitory effects on tumor cell growth in vitro and in vivo, which is dependent on the direct effect on cancer cells, has attracted considerable attention. This study examined the effects of SFN on the growth of human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells. The results showed that SFN inhibits the viability of both HeLa and HepG2 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies and the accumulation of the sub-G1 phase. RT-PCR and immunoblotting showed that treating the cells with SFN caused the down-regulation of anti-apoptotic Bcl-2 and Bcl-XL, and the up-regulation of pro-apoptotic Bax expression. SFN-induced apoptosis was associated with the proteolytic activation of caspase-3, and the degradation/cleavage of poly (ADP-ribose) polymerase and the beta-catenin protein. z-DEVD-fmk, a caspase-3 specific inhibitor, blocked the activation of caspase-3 and increased the survival of the SFN-treated HeLa and HepG3 cells, suggesting that caspase-3 activation is essential for SFN-induced apoptosis.
Park
Soung Young
SY
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, South Korea.
Kim
Gi Young
GY
Bae
Song-Ja
SJ
Yoo
Young Hyun
YH
Choi
Yung Hyun
YH
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005434:Flow Cytometry; D006367:HeLa Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D017879:Isothiocyanates; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2; D013454:Sulfoxides; D013861:Thiocyanates; D053148:Caspase 3; C016766:sulforaphane