Abstract
Norcantharidin (NCTD), a demethylated form of cantharidin, is currently used as an anti-cancer drug in China. However, the exact anti-cancer mechanism of NCTD on human cancer cells remains poorly understood. In the present study, NCTD inhibited proliferation and DNA replication effectively in HL-60 cells. DNA replication-initiation protein Cdc6 was cleaved after 12 h treatment with NCTD. This cleavage generated a truncated Cdc6 fragment with a relative molecular weight of 49 kDa and elongated treatment with NCTD resulted in a complete loss of Cdc6. In addition, we found that Cdc6 was present in both non-chromatin- and chromatin-bound fractions in the untreated HL-60 cells, and NCTD treatment led to the cleavage of Cdc6 in both fractions. NCTD-induced cleavage of Cdc6 was prevented by pre-treatment with caspase-3 inhibitor, suggesting the involvement of caspase-3 activity in the process. Furthermore, NCTD treatment resulted in apoptotic changes including granular nuclear morphology, DNA laddering and sub-G1 arrest in HL-60 cells. In conclusion, our study reveals that NCTD can inhibit DNA replication, and induce apoptosis and caspase-3-dependent cleavage of Cdc6. The anti-cancer effect of NCTD may be closely associated with the d...Continue Reading
References
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·Y M Li, J E Casida
Dec 11, 1994·Nucleic Acids Research·M HerrmannJ R Kalden
Feb 25, 1994·Science·L ShiA H Greenberg
Sep 20, 1993·FEBS Letters·R E Honkanen
Dec 6, 1996·Science·B Stillman
Jan 1, 1996·HPB Surgery : a World Journal of Hepatic, Pancreatic and Biliary Surgery·P MackL Y Cheng
Jul 15, 1997·Cancer Letters·E B YangP O Mack
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Dutta, S P Bell
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·Z YanR S Williams
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·G H WilliamsN Coleman
May 7, 1999·The Biochemical Journal·X M ZhangB D Chen
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·W JiangT Hunter
Jan 11, 2000·Molecular and Cellular Biology·Z YanR S Williams
Sep 20, 2000·Genes & Development·B O PetersenK Helin
May 15, 2002·Molecular Biology of the Cell·Frederic BlanchardWilliam C Burhans
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Yan-Nian ChenShih-Lan Hsu
Oct 1, 2003·Molecular Biology of the Cell·Hyungshin YimSeung Ki Lee
Mar 6, 2004·Cell Death and Differentiation·B SchoriesK Bommert
Jun 24, 2004·Molecular Pharmacology·Ming-Biao YinYoucef M Rustum
Aug 17, 2004·Journal of Korean Medical Science·Wei-Wei AnTakashi Ikejima
Dec 18, 2004·Mutation Research·Sandeep Saxena, Anindya Dutta
Feb 8, 2005·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Niamh MurphyJohn J O'Leary
Feb 16, 2005·Anti-cancer Drugs·Yu-Jen ChenHui-Fen Liao
Citations
Jul 6, 2007·Chinese Medicine·Rolf RauhThomas Efferth
May 9, 2014·PloS One·Hui WangYue-Zu Fan
Jan 12, 2007·Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine·Bai LiWei Gu
Apr 21, 2011·Journal of Drug Targeting·Sisi LiHongqiang Shen
Sep 14, 2012·Expert Opinion on Drug Delivery·Xia LinXing Tang
May 23, 2012·Connective Tissue Research·Dongwu LiuXiuzhen Zhang
May 23, 2012·Cellular Signalling·Shuijun ZhangJianfeng Lu
Nov 16, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Hui-Fen LiaoCheng-Deng Kuo
Feb 16, 2010·European Journal of Medicinal Chemistry·Ali ThaqiAdam McCluskey
Dec 23, 2008·Life Sciences·Yi-Chun ChenYuh-Chi Kuo
Dec 19, 2008·Cancer Letters·Kee-Lung ChangShu-Jem Su
Dec 7, 2007·Current Opinion in Cell Biology·Sara S HookAnindya Dutta
Sep 18, 2007·Biochemical and Biophysical Research Communications·Siu-Kwong PangYee-Ping Ho
Sep 30, 2014·Developmental Biology·Mohammed El DikaJacek Z Kubiak
Nov 26, 2008·ChemMedChem·Timothy A HillAdam McCluskey
Jul 21, 2009·Chemico-biological Interactions·Yu-Jen ChenHui-Fen Liao
Jul 11, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·You-Ming JiangJia-Xu Chen
Jul 19, 2015·BMC Cancer·Xin-Ping LiYue-Zu Fan
Jan 24, 2012·Journal of Ethnopharmacology·Shengpeng WangYitao Wang
Aug 16, 2016·European Journal of Medicinal Chemistry·Zhen-Bo TangLing Hui
Aug 9, 2016·Medicine·Ming-Che ChangCheng-Deng Kuo
May 29, 2013·The American Journal of Chinese Medicine·Sansan ChenJinlong Li
Dec 7, 2016·ChemMedChem·Lawson K SpareChristopher P Gordon
Jan 19, 2018·Environmental Toxicology·Shih-Chung WangShun-Fa Yang
Nov 29, 2007·Anti-cancer Drugs·Yu-Jen ChenHui-Fen Liao
Aug 11, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric LauWei Jiang
Jun 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Arkaitz IbarraJuan Méndez
Aug 20, 2015·Anti-cancer Drugs·Ming-Che ChangCheng-Deng Kuo
Jun 10, 2020·Chinese Medicine·Mu-Su PanYue-Zu Fan
Jan 15, 2015·Anti-cancer Drugs·Ming-Che ChangCheng-Deng Kuo