| Summary: | 碩士 === 中山醫學大學 === 醫學研究所 === 101 === Currently, the most common strategy to treatment of acute myeloid leukemia is to induce apoptosis and differentiation of this tumor cells. The addition of differentiation induction therapy with all trans-retinoic acid (ATRA) is now regarded as mandatory in the treatment of acute promyelocytic leukemia (APL) with a good complete remission rate, but some severe side effects mediated by ATRA are challenge to be overcome. Therefore, seek effective drug, and lower side effects of therapy are essential issues for AML treatment. Lauryl ester of gallic acid (lauryl gallate) is commonly used as an antioxidant of food additives. lauryl gallate has anti-inflammatory and anti-cancer effects. This study aimed to explore the effect of lauryl gallate on the reactivity of ATRA in both APL and non-APL AML cells in vitro using human AML cell lines, HL-60 and KG-1. Results showed that 1μM ATRA combined with 3μM lauryl gallate significantly induced differentiation of HL60 and KG-1 cells comfirmed by morphological changes and increase of CD14 and CD11b monocytic surface marker expression. Our data also exhibited that ATRA plus lauryl gallate treatment induced apoptosis in a dose- and time-dependent manner. Data from Western blot analysis indicated that combined treatment with ATRA and
lauryl gallate decreased the expression levels of anti-apoptotic molecules Bcl-2 and Mcl-1, and increased the level of proapoptotic molecules PUMA, Bak and Bax. At the meanwhile, caspase -2,-3,-6,-8 and -9 were activated by combined treatment. Over all, our observations showed that ATRA combined with lauryl gallate could induce human AML HL-60 and KG-1 cell toward both neutrophil and monocyte differentiation. In addition, ATRA plus lauryl gallate treatment also triggered AML cell apoptosis through Bcl-2 family molecule-dependent mitochondrion pathway. Based on these findings, we demonstrate that ATRA plus lauryl gallate will have the development potential of anti-cancer combined treatments. These results suggest that lauryl gallate might have the potential to combine used with ATRA as a therapeutic regimen in AML patients.
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