Abstract 1031: The effects of NT1014, a novel AMPK activator, on ovarian cancer cell proliferation and apoptosis.

Abstract

Abstract Introduction: Anti-diabetic biguanide drugs, such as metformin, have been shown to have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors. NT1014 (NovaTarg Therapeutics) is a novel AMPK activator that enters cells specifically through the organic cation transporter, OCT1. Thus, we sought to assess the effect of NT1014 on cell proliferation and apoptosis in human ovarian cancer cell lines. Methods: Ovarian cancer cell proliferation was assessed by MTT assay after exposure to NT1014. Apoptosis was analyzed by Annexin V-FITC assay. Cell cycle progression was evaluated by Cellometer. Phosphorylated-S6, pan-S6, and OCT1 were evaluated by Western immunoblotting analysis. Results: NT1014 significantly inhibited proliferation in a dose-dependent manner in both ovarian cancer cell lines (IC50 1000 μM for SKOV3, 500 μM for IGROV1), within 48 hours of exposure. Treatment with NT1014 resulted in G1 cell cycle arrest in both cell lines. Apoptosis occurred in IGROV1 cells exposed to NT1014, but not in SKOV3 cells. Western immunoblot analysis demonstrated that NT1014 decreased phosphorylation of the S6 protein, a key downstream target of the mTOR pathway. Expression of OCT1 was also decreased in a dose-dependent fashion. Conclusion: NT1014 suppressed ovarian cancer cell growth, predominantly through G1 cell cycle arrest, and resulted in inhibition of the mTOR pathway. More work is needed to determine if metformin and related novel agents, such as NT1014, will be beneficial in the treatment of women with ovarian cancer. Citation Format: Joshua Kilgore, Amanda L. Jackson, Haifeng Qiu, Chunxiao Zhou, Kenneth Batchelor, Paola Gehrig, Victoria Bae-Jump. The effects of NT1014, a novel AMPK activator, on ovarian cancer cell proliferation and apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1031. doi:10.1158/1538-7445.AM2013-1031