Apoptotic and anti-proliferative effects of 17beta-estradiol and 17beta-estradiol-like compounds in the Hep3B cell line.
Since there is evidence for estrogen and estrogen-like compounds to have beneficial effect on the pathogenesis of hepatocellular carcinoma (HCC), this study was designed to investigative the apoptotic and anti-proliferative effects of these compounds on the human hepatoma Hep3B cell line. The Hep3B cells were treated with 17beta-estradiol (E2), diethylstilbestrol (DES), tamoxifen, and genistein. After treatments of these compounds at the concentration of 10(-6) or 10(-8) M, the Hep3B cells were demonstrated to have significant DNA fragmentation, nucleus condensation, cytochrome-c leaking from the mitochondria and caspase-3 activation by DAPI and Western blotting. The cells were also observed to have declined proliferative potential by MTT assay, arrested cell cycle by flow-cytometry measurements. However, the cytochrome-c leaking from the mitochondria induced by E2 and E2-like compounds was blocked totally by ICI 182,780 treatment. These finding suggest that estrogen and the estrogen-like compounds may induce anti-proliferative and apoptotic effects in Hep3B cells, and the E2 and the E2-like compounds mediated apoptotic effect was estrogen receptor dependent. Among the drugs tested, E2, E2 agonists (DES and genistein) and partial antagonist (tamoxifen), all showed the stronger anti-tumor potential.
Huang
Erh-Jung
EJ
Center of General Education, Central Taiwan, University of Science and Technology, 406 Taichung, Taiwan.
Wu
Cheng-Chung
CC
Huang
Hsien-Ping
HP
Liu
Jer-Yuh
JY
Lin
Chung-Sheng
CS
Chang
Yan-Zin
YZ
Lin
James A
JA
Lin
Jaung-Geng
JG
Chen
Li-Mien
LM
Lee
Shin-Da
SD
Kuo
Wei-Wen
WW
Huang
Chih-Yang
CY
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects
D004968:Estrogens, Non-Steroidal; D004958:Estradiol; D004054:Diethylstilbestrol; D019833:Genistein