Abstract 3794: Mechanistic studies on the anti-tumor effect of jacaric acid on murine macrophage-like leukemia PU5-1.8 cells

Abstract

Abstract This study aims at demonstrating the in vitro and in vivo anti-tumor effect and action mechanisms of jacaric acid, a conjugated linolenic acid isomer which is present in jacaranda seed oil, on murine macrophage-like leukemia PU5-1.8 cells. Our results demonstrated the growth-inhibitory effect of jacaric acid on PU5-1.8 cells in a time- and concentration-dependent manner, as measured by MTT reduction and fluorometric cell proliferation assays, while it exerted minimal cytotoxicity on normal murine cells. Pre-treatment of PU5-1.8 cells with jacaric acid significantly decreased the leukemic cell growth in syngeneic BALB/c mice, while consumption of jacaric acid is apparently non-toxic to the mice. Flow cytometric analysis revealed the induction of G0/G1 cell cycle arrest, accompanied by a decrease in cyclin E and CDK2 proteins as demonstrated by Western blotting. Jacaric acid also triggered apoptosis in PU5-1.8 cells as reflected by induction of DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization, which was quantified by ELISA, Annexin V assay and JC-1 dye staining method, respectively. Up-regulation of Bax and down-regulation of Bcl-2 and Bcl-xL proteins might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of jacaric acid on PU5-1.8 cells might be mediated through inducing cell cycle arrest and apoptosis of the leukemia cells. Therefore, jacaric acid represents a naturally-occurring potential candidate for the treatment of some forms of myeloid leukemia with minimal toxicity and fewer side effects. Citation Format: Wai Nam Liu, Kwok Nam Leung. Mechanistic studies on the anti-tumor effect of jacaric acid on murine macrophage-like leukemia PU5-1.8 cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3794. doi:10.1158/1538-7445.AM2015-3794