Lee J.Huang M.-S.Yang I.-C.Lai T.-C.Wang J.-L.Pang V.F.Hsiao M.YEN-PING KUO2021-07-052021-07-0520080006-291Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-46349111715&doi=10.1016%2fj.bbrc.2008.03.149&partnerID=40&md5=36a3fa87ecbc4fa94bafd81f33da3106https://scholars.lib.ntu.edu.tw/handle/123456789/569190In 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. ? 2008 Elsevier Inc. All rights reserved.[SDGs]SDG3acetylcysteine; antioxidant; caspase 8; caspase 9; glutathione; protein Bax; protein p53; rotenone; tiron; apoptosis; article; cancer cell culture; cell cycle; cell cycle arrest; cell cycle G2 phase; cell cycle M phase; cell proliferation; cell type; controlled study; cytotoxicity; DNA content; dose response; enzyme activation; fibroblast; flow cytometry; human; human cell; mouth cancer; mouth mucosa; priority journal; protein function; protein targeting; Western blotting; Antineoplastic Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 8; Caspase 9; Cell Division; Cell Line, Tumor; Cell Proliferation; Cytochromes c; G2 Phase; Humans; Mouth Neoplasms; Rotenone; Tumor Suppressor Protein p53journal article10.1016/j.bbrc.2008.03.149184027712-s2.0-46349111715