title: Xanthorrhizol induces apoptosis through ROS-mediated MAPK activation in human oral squamous cell carcinoma cells and inhibits DMBA-induced oral carcinogenesis in hamsters.
abstract: Xanthorrhizol, a natural sesquiterpenoid compound isolated from Curcuma xanthorrhiza Roxb, has been known to inhibit the growth of human colon, breast, liver and cervical cancer cells. In this study, xanthorrhizol decreased cell viability, induced apoptosis and decreased the level of full-length PARP in SCC-15 oral squamous cell carcinoma (OSCC) cells. A decrease in cell viability and PARP degradation was not prevented by treatment with the caspase inhibitor Z-VAD-fmk in xanthorrhizol-treated cells. Xanthorrhizol treatment elevated intracellular Ca(2+) and ROS levels in SCC-15 cells. Treatment with a Ca(2+) chelator, EGTA/AM, did not affect xanthorrhizol- induced cytotoxicity, but cell viability was partly recovered by treatment with endogenous antioxidant, GSH, or hydroxy radical trapper, MCI-186. Furthermore, the viability of xanthorrhizol-treated SCC-15 cells was significantly restored by treatment with SB203580 and/or SP600125 but not significantly by PD98059 treatment. Xanthorrhizol-induced activation of p38 MAPK and JNK was blocked by MCI-186. Finally, xanthorrhizol suppressed the number of tumors in buccal pouches and increased the survival rate in hamsters treated with 7,12-dimethylbenz[a]anthracene. In conclusion, xanthorrhizol may induce caspase-independent apoptosis through ROS-mediated p38 MAPK and JNK activation in SCC-15 OSCC cells and prevent chemical-induced oral carcinogenesis. Therefore, xanthorrhizol seems to be a promising chemopreventive agent.
authors.affiliation: Department of Oral Biology, Brain Korea 21 Project, Yonsei University College of Dentistry, Seoul, Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Jeong Mi
authors.initials: JM
authors.lastname: An
authors.forename: Won-Yoon
authors.initials: WY
authors.lastname: Chung
authors.forename: Kwang-Kyun
authors.initials: KK
authors.lastname: Park
authors.forename: Jae Kwan
authors.initials: JK
authors.lastname: Hwang
authors.forename: Du Sik
authors.initials: du S
authors.lastname: Kim
authors.forename: Su Ryeon
authors.initials: SR
authors.lastname: Seo
authors.forename: Jeong Taeg
authors.initials: JT
authors.lastname: Seo
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D006224:Cricetinae; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D010636:Phenols; D017382:Reactive Oxygen Species; C120248:xanthorrhizol; D015127:9,10-Dimethyl-1,2-benzanthracene