ApoG2, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces apoptosis and suppresses tumor growth in nasopharyngeal carcinoma xenografts

International Journal of Cancer. Journal International Du Cancer
Zhe-Yu HuYi-Xin Zeng

Abstract

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China. It has been reported that overexpression of antiapoptotic Bcl-2 family proteins in NPC has caused the lack of long-term efficacy of conventional therapies. Apogossypolone (ApoG2), a novel small-molecule inhibitor of antiapoptotic Bcl-2 family proteins, has been discovered as the optimized derivative of gossypol. In this study, we found that in NPC cells, ApoG2 totally blocked the antiapoptotic function of Bcl-2 family proteins without affecting the expression levels of these proteins. ApoG2 selectively inhibited proliferation of 3 NPC cell lines (C666-1, CNE-1 and CNE-2) that highly expressed the antiapoptotic Bcl-2 proteins. This inhibitory activity was associated with release of cytochrome c, activation of caspase-9 and caspase-3 and apoptosis of sensitive NPC cells. However, ApoG2 had no obvious inhibitory effect on NPC cell line HONE-1, which expressed antiapoptotic Bcl-2 and Bcl-xL at a low level. We further found that ApoG2 effectively suppressed tumor growth of NPC xenografts in nude mice and enhanced the antitumor effect of CDDP (cisplatin) on NPC cells in vitro and in vivo. Immunohistochemical results showed that the expression of CD31 decreased...Continue Reading

References

Aug 11, 1991·Nucleic Acids Research·P W LairdA Berns
Mar 1, 1985·The Laryngoscope·R I Dickson, A D Flores
Jan 2, 1993·International Journal of Cancer. Journal International Du Cancer·Q L LuJ A Thomas
Feb 8, 1996·Nature·E H ChengJ M Hardwick
Jul 17, 1997·Nature·Q L DeverauxJ C Reed
Apr 29, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M Al-SarrafJ F Ensley
Aug 15, 1998·Trends in Cell Biology·A Kelekar, C B Thompson
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·J L WangZ Huang
Dec 6, 2000·Life Sciences·X WangS W Tsa
Feb 15, 2001·Nature Cell Biology·S P TzungD M Hockenbery
Apr 20, 2001·Clinical Otolaryngology and Allied Sciences·A L McDermottJ C Watkinson
Jul 18, 2001·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·R L Ornberg
Jun 28, 2002·Cancer Cell·Douglas R Green, Gerard I Evan
Nov 27, 2002·Seminars in Cancer Biology·Nancy Raab-Traub
Jan 28, 2004·Cell·Nika N Danial, Stanley J Korsmeyer
Jul 9, 2004·European Journal of Medicinal Chemistry·Vi-Thuy DaoRobert J Michelot
Dec 1, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher L OliverCarol R Bradford
May 20, 2005·Nature·Tilman OltersdorfSaul H Rosenberg
Feb 16, 2006·International Journal of Cancer. Journal International Du Cancer·Jill LacyYung-Chi Cheng
Oct 5, 2006·Cancer Research·Jian-Zhong QinBrian J Nickoloff
Oct 13, 2006·Journal of Medicinal Chemistry·Guoping WangShaomeng Wang
Apr 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ramzi M MohammadAyad Al-Katib
Jun 29, 2007·International Journal of Cancer. Journal International Du Cancer·Ching-Huai KoYen-Chou Chen
Jul 5, 2007·BMC Cancer·Vijaya L DamarajuHenriette Gourdeau

❮ Previous
Next ❯

Citations

Jan 19, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ying-Xue WangChang-Mei Liu
Mar 6, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lei ZhaoMeng-Zhong Liu
Dec 27, 2011·Expert Opinion on Therapeutic Patents·Naval BajwaZaneta Nikolovska-Coleska
Sep 4, 2010·Expert Opinion on Emerging Drugs·Asfar S AzmiFazlul H Sarkar
May 5, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Haseeb ZubairS M Hadi
Dec 30, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lijun YeJian Sun
Nov 3, 2009·Advances in Food and Nutrition Research·Xi WangYueming Jiang
Jul 20, 2017·Future Medicinal Chemistry·Yuzhi LuWei Wang
Apr 3, 2009·Archiv der Pharmazie·Yonghua ZhanLiang Xu
May 27, 2017·Current Medicinal Chemistry·Yun ZengDaocheng Wu
Jul 26, 2014·Molecular Medicine Reports·Xianqing ZhangXiaofeng Huang
May 18, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Yong-Hua ZhanXian-Qing Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis