Format

Send to

Choose Destination
Int J Cancer. 2008 Nov 15;123(10):2418-29. doi: 10.1002/ijc.23752.

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

Author information

1
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.

Erratum in

  • Int J Cancer. 2009 Jan 15;124(2):510.

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 after ApoG2 treatment, which suggested inhibition of angiogenesis in NPC xenografts. Our findings strongly suggest that ApoG2 may serve as a novel inhibitor of Bcl-2 family proteins and, by targeting these proteins, may become a promising drug for the treatment of NPC.

PMID:
18712728
DOI:
10.1002/ijc.23752
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center