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Xanthorrhizol Induces Apoptosis Through ROS-Mediated MAPK Activation in Human Oral Squamous Cell Carcinoma Cells and Inhibits DMBA-Induced Oral Carcinogenesis in Hamsters

Authors
 Ju Yeon Kim  ;  Jeong Mi An  ;  Won-Yoon Chung  ;  Kwang-Kyun Park  ;  Jae Kwan Hwang  ;  Du Sik Kim  ;  Su Ryeon Seo  ;  Jeong Taeg Seo 
Citation
 Phytotherapy Research, Vol.27(4) : 493-498, 2013 
Journal Title
 Phytotherapy Research 
ISSN
 0951-418X 
Issue Date
2013
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 Ca2+ and ROS levels in SCC-15 cells. Treatment with a Ca2+ 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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86627
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/ptr.4746/abstract
DOI
10.1002/ptr.4746
Appears in Collections:
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실)
Yonsei Authors
박광균(Park, Kwang Kyun)
서정택(Seo, Jeong Taeg) ORCID logo https://orcid.org/0000-0003-2697-0251
정원윤(Chung, Won Yoon) ORCID logo https://orcid.org/0000-0001-8428-9005
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