In vitro effects on proliferation, telomerase activity and apoptosis of an eremophilanoid sesquiterpene from Senecio oldhamianus maxim in cultured human tumor cell lines.
8,11-Dioxol-6-en-9alpha, 10alpha-epoxy-8beta-hydroxyeremophilane (HEM), a new eremophilanoid sesquiterpene, was isolated from Senecio oldhamianus Maxim. Its effects of cytotoxicity, telomerase activity, apoptosis and related genes expression in two human tumor cell lines, human hepatoma cells SMMC-7721 and human oophoroma cells HO-8910, were studied. Hydroxycamptothecine (HCPT) was used as a positive control. The IC50 of cytotoxicity by HEM were 24.9 +/- 2.1 and 19.4 1.6 microM in SMMC-7721 and HO-8910 cells respectively, and 0.35 +/- 0.10 and 0.27 +/- 0.08 microM for HCPT. HEM inhibited telomerase activity with the IC50 35.9 +/- 3.2 microM in SMMC-7721 and 25.6 +/- 2.6 microM in HO-8910 cells, while HCPT had no effect on telomerase activity in both tumor cell lines. HEM 20-30 microM induced apoptosis in SMMC-7721 cells from 5.7% to 18.4% and in HO-8910 cells from 7.6% to 67.1%. While HCPT 0.1-0.5 microM induced apoptosis in SMMC-7721 cells from 6.5% to 13.3% and in HO-8910 cells from 9.9% to 30.9%. HEM 30 microM significantly decreased Bcl-2 protein expression to 58.7% in SMMC-7721 and to 57.6% in HO-8910 cells. While HCPT 0.5 microM significantly decreased Bcl-2 protein expression to 64.3% in SMMC-7721 and to 70.0% in HO-8910 cells. HEM 25 microM and 30 microM significantly increased P53 protein expression 2.3-3.6-fold in SMMC-7721 and 3.0-5.7- fold in HO-8910 cells. While HCPT 0.5 microM significantly increased P53 protein expression 3.3-fold in SMMC-7721 and 2.7-fold in HO-8910 cells. Overall, HCPT exhibited a more potent effect on cytotoxicity and apoptosis in the two tumor cell lines than HEM did. However HEM can inhibit telomerase activity in the two tumor cell lines but HCPT cannot.
Wang
Chun-Ming
CM
School of Life Sciences, Lanzhou University, Lanzhou, China.
Yang
Hua
H
Wei
Ya-Ming
YM
Jia
Zhong-Jian
ZJ
Zheng
Rong-Liang
RL
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005434:Flow Cytometry; D019254:Genes, bcl-2 / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012674:Senecio / Q000737:chemistry*; D012717:Sesquiterpenes / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors*; D015854:Up-Regulation / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D012717:Sesquiterpenes; D019098:Telomerase