Essential roles of caspases and their upstream regulators in rotenone-induced apoptosis.
In the present study, we examined whether caspases and their upstream regulators are involved in rotenone-induced cytotoxicity. Rotenone significantly inhibited the proliferation of oral cancer cell lines in a dose-dependent manner compared to normal oral mucosal fibroblasts. Flow cytometric analysis of DNA content showed that rotenone treatment induced apoptosis following G2/M arrest. Western blotting showed activation of both the caspase-8 and caspase-9 pathways, which differed from previous studies conducted in other cell types. Furthermore, p53 protein and its downstream pro-apoptotic target, Bax, were induced in SAS cells after treatment with rotenone. Rotenone-induced apoptosis was inhibited by antioxidants (glutathione, N-acetylcysteine, and tiron). In conclusion, our results demonstrate significant involvement of caspases and their upstream regulators in rotenone-induced cytotoxicity.
Lee
Jihjong
J
Graduate Institute of Veterinary Medicine, College of Biological Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
Huang
Ming-Shyan
MS
Yang
I-Chi
IC
Lai
Tsung-Ching
TC
Wang
Jui-Ling
JL
Pang
Victor Fei
VF
Hsiao
Michael
M
Kuo
Mark Y P
MY
D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8 / Q000032:analysis / Q000378:metabolism*; D053453:Caspase 9 / Q000032:analysis / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000201:enzymology / Q000378:metabolism*; D012402:Rotenone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D012402:Rotenone; D045304:Cytochromes c; D053181:Caspase 8; D053453:Caspase 9