The vitamin E derivative gamma tocotrienol promotes anti-tumor effects in acute myeloid leukemia cell lines. (c2019)

Abstract

Acute Myeloid Leukemia (AML) is a type of cancer characterized by the formation of faulty myelogenous cells with morphological heterogeneity and cytogenic aberrations leading to a total loss of their function. In the midst of the struggle to find an effective and safe AML treatment, vitamin E derivatives, mainly tocopherols were previously considered as potential anti-tumor compounds. Recently, other isoforms of vitamin E, namely tocotrienols have been proposed as potential potent anti-cancerous agents, displaying promising therapeutic effects in different cancer types. The aim of the present study is to investigate the anti-cancerous effect of γ-tocotrienol, through examining the extent of its effects on the growth of human-derived AML cell lines in vitro, and deciphering the underlying molecular mechanisms. This was achieved by performing MTS cell viability assays, propidium iodide (PI) based cell cycle analysis, flow cytometry-based annexin V/PI apoptosis staining assay, cell death detection ELISA, western immunoblotting, and reactive oxygen species detection assay. Analysis of our results show that γ-tocotrienol exhibits time and dose-dependent anti-proliferative, pro-apoptotic and antioxidant effects on U937 and KG-1 cell lines, through the upregulation of several proteins involved in the intrinsic apoptotic pathway.