Cytotoxic effects and pro-apoptotic mechanism of TBIDOM, a novel dehydroabietylamine derivative, on human hepatocellular carcinoma SMMC-7721 cells.
We have investigated the antiproliferative effects of TBIDOM (N-(4-(2,2,2-trifluoroethyl) benzylidene) (7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl) meth-anamine) and have explored its possible mechanisms on human hepatocellular carcinoma SMMC-7721 cells. The proliferative status of cells treated with TBIDOM was measured by the colorimetric MTT assay. Cellular apoptosis was analysed using Hoechst 33342 staining and flow cytometry. Reduction of mitochondrial membrane potential (Delta psi(m)) was also detected by flow cytometry. Western blotting assay was used to evaluate the release of cytochrome c and expression of p53, Bcl-2 and Bax proteins. It was shown that TBIDOM displayed a significant inhibitory effect on growth of SMMC-7721 cells in a dose- and time-dependent manner. Hoechst 33342 staining and flow cytometry analysis showed an increase of apoptosis rate and decrease of mitochondrial membrane potential after SMMC-7721 cells were exposed to TBIDOM for 24 h. Pretreatment of SMMC-7721 cells with TBIDOM significantly induced a decrease of Bcl-2 protein expression and an increase of caspase-3 activity and Bax protein expression. The results indicated that TBIDOM could effectively inhibit proliferation by induction of apoptosis and could be a promising candidate in the development of a novel class of antitumour agent.
Li
Fu
F
Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, JiangSu Province, The People's Republic of China.
He
Ling
L
Song
Zhan-Qian
ZQ
Yao
Jin-Cheng
JC
Rao
Xiao-Ping
XP
Li
Hai-Tao
HT
D045784:Abietanes / Q000008:administration & dosage / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003124:Colorimetry; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
C527614:(N-(4-(2,2,2-trifluoroethyl) benzylidene) (7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl) meth-anamine); D045784:Abietanes; D000970:Antineoplastic Agents; D001593:Benzyl Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3