Sensitization of pancreatic cancer cells to ApoG2 induced killing by curcumin

Abstract

13152 Background: In pancreatic cancer, several important survival molecules such as NF-kappa B and Bcl-2 or Bcl-XL are highly activated. Thus agents that inhibit NF-KappaB activation, together with agents that inhibit Bcl-2 or Bcl-XL protein function, may lead to enhanced cell killing. ApoG2, a new derivative of natural product gossypol, is a potent small molecule inhibitor of Bcl-2 and Bcl-XL proteins. Curcumin, an active ingredient from the rhizome of the plant, Curcuma longa, has anti-inflammatory and anti-cancer activities and works by inactivation of NF-Kappa B activity. In this study we have investigated the effects of curcumin on ApoG2 induced apoptosis. Methods: The BxPC-3 human pancreatic cancer cell line was used in this study. ApoG2 was dissolved in DMSO at 1 mM stock solution, and curcumin was dissolved in DMSO at 20 mM stock solution. Cell viability was determined by the standard MTT assay and apoptosis was measured by histone/DNA ELISA method. Results: Pretreatment of human pancreatic cell line BxPC-3 with curcumin sensitizes ApoG2 induced cell killing. In the dose escalation with ApoG2 at 48 hrs on MTT assay, 250 nM showed 75% cell viability, while 2.5 uM of curcumin at 72 hrs showed 80% cell viability. Pretreatment with curcumin for 24 hrs followed by ApoG2 at 48 hrs showed 55% cell viability (p = 0.0005). Apoptosis by histone/DNA ELISA showed 4-fold induction of cell death with ApoG2 at 48 hrs, 7-fold induction of cell death with curcumin at 72 hrs. However, pretreatment with curcumin for 24 hrs followed by ApoG2 at 48 hrs showed 10-fold induction in apoptosis compared to the control. Conclusions: From these results, we conclude that curcumin enhanced ApoG2 induced cell growth inhibition and apoptosis of BxPC-3 cells. No significant financial relationships to disclose.