Jacaric acid inhibits the growth of murine macrophage-like leukemia PU5-1.8 cells by inducing cell cycle arrest and apoptosis

BACKGROUND: Conjugated linolenic acids (CLN) refer to the positional and geometric isomers of octadecatrienoic acids with three conjugated double bonds (C18:3). Previous researches have demonstrated that CLN can inhibit the growth of a wide variety of cancer cells, whereas the modulatory effect of CLN on various myeloid leukemia cells remains unclear. This study aims at demonstrating the in vitro anti-tumor effect and action mechanisms of jacaric acid, a CLN isomer which is present in jacaranda seed oil, on the murine macrophage-like leukemia PU5-1.8 cells. METHODS AND RESULTS: It was found that jacaric acid inhibited the proliferation of PU5-1.8 cells in a time- and concentration-dependent manner, as determined by the MTT reduction assay and by using CyQUANT(®) NF Cell Proliferation Assay Kit, while it exerted minimal cytotoxicity on normal murine cells. Besides, the reactive oxygen species production in jacaric acid-treated PU5-1.8 cells was elevated in a concentration-dependent mannar. Flow cytometric analysis revealed the induction of G(0)/G(1) cell cycle arrest, accompanied by a decrease in CDK2 and cyclin E proteins. Jacaric acid also triggered apoptosis as reflected by induction of DNA fragmentation, phosphatidylserine externalization, mitochondrial membrane depolarization, up-regulation of pro-apoptotic Bax protein and down-regulation of anti-apoptotic Bcl-2 and Bcl-x(L) proteins. CONCLUSIONS: Our results demonstrated the growth-inhibitory effect of jacaric acid on PU5-1.8 cells through inducing cell cycle arrest and apoptosis, while exhibiting minimal cytotoxicity to normal murine cells. Therefore, jacaric acid is a potential candidate for the treatment of some forms of myeloid leukemia with minimal toxicity and fewer side effects.