MMPT: a thiazolidin compound inhibits the growth of lung cancer H1792 cells via Fas-mediated and caspase-dependent apoptosis pathway.
MMPT, a thiazolidin compound, was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. However, the related mechanism has yet not been revealed. In this study, we investigated the cellular and molecular events underlying the antitumor function of this compound in human lung adenocarcinoma H1792 cells, focusing on the early cytotoxic effect. Treatment of H1792 cancer cells with MMPT (0.1-100 microM for 24-72 h) resulted in a growth inhibition in a dose and time-dependent manner, determined by MTT assay. This effect was accompanied by apoptosis, evidenced by Nucleosome ELISA, H33258 stained assay, and Sub-G1 analysis. Our data showed that MMPT caused activation of caspase-3, caspase-6 and caspase-8, but not caspase-9. The finding that MMPT induced apoptosis through a membrane-mediated mechanism was supported by the up-regulated expression of Fas (CD95/APO-1), and Fas ligand. Overall, our results demonstrated that MMPT induced growth inhibition of H1792 cells through a Fas-mediated and caspase-dependent apoptosis pathway, which suggested that MMPT might be used as a Fas/FasL and caspases promoter to initiate lung cancer cell apoptosis.
Zhao
Yun-feng
YF
School of Life Science, Qufu Normal University, No.57 Jingxuan West Road, Qufu 273165, China. zhaoyf1989@yahoo.com.cn
Li
Xiu-lan
XL
Sun
Yu-xi
YX
Niu
Wen
W
Hu
Zun-li
ZL
Lin
Lin
L
Kong
Qing-zhong
QZ
D000814:Aniline Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D053222:Fas Ligand Protein / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
C503119:5-((4-methylphenyl)methylene)-2-(phenylamino)-4(5H)-thiazolone; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D006131:Growth Inhibitors; D013844:Thiazoles; D019014:fas Receptor; D020169:Caspases