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PLoS One

Title:		Cudrania tricuspidata Stem Extract Induces Apoptosis via the Extrinsic Pathway in SiHa Cervical Cancer Cells
Author(s):		Kwon SB; Kim MJ; Yang JM; Lee HP; Hong JT; Jeong HS; Kim ES; Yoon DY;
Address:		"Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea. Department of Chemistry, University of Minnesota, Twin Cities, Minneapolis, MN, 55455, United States of America. College of Pharmacy, Medical Research Center, Chungbuk National University, Osong, Chungbuk, Korea. Agriculture, Life and Environments Sciences, Chungbuk National University, Cheongju, Chungbuk, Korea. Chungcheongbukdo Bio CS, Osong, Chungbuk, Korea"
Journal Title:		PLoS One
Year:		2016
Volume:		20160309
Issue:		3
Page Number:		e0150235 -
DOI:		10.1371/journal.pone.0150235
ISSN/ISBN:		1932-6203 (Electronic) 1932-6203 (Linking)
Abstract:		"The focus of this study is the anti-cancer effects of Cudrania tricuspidata stem (CTS) extract on cervical cancer cells. The effect of CTS on cell viability was investigated in HPV-positive cervical cancer cells and HaCaT human normal keratinocytes. CTS showed significant dose-dependent cytotoxic effects in cervical cancer cells. However, there was no cytotoxic effect of CTS on HaCaT keratinocytes at concentrations of 0.125-0.5 mg/mL. Based on this cytotoxic effect, we demonstrated that CTS induced apoptosis by down-regulating the E6 and E7 viral oncogenes. Apoptosis was detected by DAPI staining, annexin V-FITC/PI staining, cell cycle analysis, western blotting, RT-PCR, and JC-1 staining in SiHa cervical cancer cells. The mRNA expression levels of extrinsic pathway molecules such as Fas, death receptor 5 (DR5), and TNF-related apoptosis-inducing ligand (TRAIL) were increased by CTS. Furthermore, CTS treatment activated caspase-3/caspase-8 and cleavage of poly (ADP-ribose) polymerase (PARP). However, the mitochondrial membrane potential and expression levels of intrinsic pathway molecules such as Bcl-2, Bcl-xL, Bax, and cytochrome C were not modulated by CTS. Taken together, these results indicate that CTS induced apoptosis by activating the extrinsic pathway, but not the intrinsic pathway, in SiHa cervical cancer cells. These results suggest that CTS can be used as a modulating agent in cervical cancer"
Keywords:		"Apoptosis/*drug effects Cell Cycle/drug effects Cell Line, Tumor Cell Shape/drug effects Chromatography, High Pressure Liquid Down-Regulation/drug effects Female Humans Keratinocytes/cytology/drug effects Moraceae/*chemistry Oncogene Proteins, Viral/genet;"
Notes:		"MedlineKwon, Sae-Bom Kim, Min-Je Yang, Jin Mo Lee, Hee-Pom Hong, Jin Tae Jeong, Heon-Sang Kim, Eun Suk Yoon, Do-Young eng Research Support, Non-U.S. Gov't 2016/03/10 PLoS One. 2016 Mar 9; 11(3):e0150235. doi: 10.1371/journal.pone.0150235. eCollection 2016"