Abstract 3447: Obatoclax analogue SC-2001 induced autophagy through SHP1/STAT3 pathway in hepatocelluar carcinoma.

Abstract

Abstract Obatoclax induced cancer cells apoptosis through targeting anti-Bcl-2 family. Previously, we have generated 20 obatoclax analogues with three synthetic steps and tested cytotoxicity in HCC cell lines. Among these analogues, SC-2001 not only inhibited anti-Bcl-2 family activity but also reduced STAT3 phosphorylation and subsequently repressed transcriptional activity of STAT3 targeting genes. Here, we further revealed that SC-2001 induced LC3-II with time and dose dependent manner in HCC cell line. We also observed that autophogosomes were induced with SC-2001 treated cells under electron microscope detection. Conversely, sodium vanadate, a phosphatase inhibitor, abolished the LC3 induction and autophagic effect in SC-2001 treated cells. In addition, overexpression of STAT3 in PLC5 cells attenuate autophagic effect with SC-2001 treatment. Genetic knockdown of SHP-1, a negative regulator of STAT3, by siRNA reduced autophagy induced by SC-2001. In summary, our data suggested that SC-2001 can induce autophagic cell death through, at least in part, SHP-1/STAT3 signaling pathway. (Supported by NSC-100-2325-B-010-007) Citation Format: Jung-Chen Su, Chun-Yu Liu, Wei-Tien Tai, Kuen-Feng Chen, Chung-Wai Shiau. Obatoclax analogue SC-2001 induced autophagy through SHP1/STAT3 pathway in hepatocelluar carcinoma. [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 3447. doi:10.1158/1538-7445.AM2013-3447