Abstract

BackgroundConjugated 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 resultsIt 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 G0/G1 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-xL proteins.ConclusionsOur 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.

Highlights

  • Conjugated linolenic acids (CLN) refer to the positional and geometric isomers of octadecatrienoic acids with three conjugated double bonds (C18:3)

  • Conjugated linolenic acids inhibit the proliferation of the murine macrophage‐like leukemia cells To measure the anti-proliferative effect of CLN isomers on PU5-1.8 cells, the MTT reduction assay was performed

  • Since jacaric acid was found to be the most potent isomer among all the six CLN isomers tested, it was chosen as the specific target for further investigation of its anti-leukemic activity on PU5-1.8 cells

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Summary

Introduction

Conjugated linolenic acids (CLN) refer to the positional and geometric isomers of octadecatrienoic acids with three conjugated double bonds (C18:3). Accumulating evidences have demonstrated the growth-inhibitory effects of CLN on a wide variety of human cancer cell lines in vitro, which include hepatoma HepG2 cells, lung adenocarcinoma A549 cells, breast adenocarcinoma MCF-7 cells, stomach tubular adenocarcinoma MKN-7 cells, colon carcinoma DLD-1 cells, bladder cancer T24 cells and prostate cancer LNCaP and PC-3 cells [9, 12, 16, 17]. Their anti-tumor effect, action mechanisms and therapeutic potential on various types of myeloid leukemia cells remain poorly understood

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