Britannin a Sesquiterpene Lactone from Inula aucheriana Exerted an Anti-leukemic Effect in Acute Lymphoblastic Leukemia (ALL) Cells and Enhanced the Sensitivity of the Cells to Vincristine

Abstract

Since chemotherapy drugs have dose-related side effects, there is still a need for finding new agents with suitable cytotoxic effects without any harmful effects. For this purpose, we evaluated the cytotoxic effects of Britannin that is a Sesquiterpene Lactone compound Inula aucheriana, alone or in combination with Vincristine (VCR), on Acute Lymphoblastic Leukemia (ALL)-derived MOLT-4 cells. In this study, we found that Britannin decreased the viability of MOLT-4 cells with the IC50 Values of 2 µM, but had no cytotoxic effects on normal cells or Peripheral Blood Mononuclear Cells (PBMCs). Our results also showed that Britannin decreased the proliferation of MOLT-4 cells by preventing the transition of the cells from the S phase of the cell cycle through the up-regulation of p21 and p27. Moreover, this agent induced ROS-mediated apoptosis by altering the expression of Bax, Bim, Caspase3, Bcl2, and XIAP. Britannin also produced a synergistic effect with Vincristine in MOLT-4 cells. Taken together, the results of this study showed for the first time that Britannin, as a natural Sesquiterpene Lactone, has cytotoxic effects that could be considered as an anti-leukemic agent in the treatment of ALL. However, there is still a demand for further studies that examine the efficacy and the safety of this purified compound.