Leukemia is one of the highly lethal
cancers among all pediatric
cancers. With limited
drug options and the severe side effects associated with the current
chemotherapy, there is pressing need to look for new and novel
anticancer agents. Against this backdrop, in the present study we evaluated the anticancer activity of a natural
coumarin,
marmesin against human
leukemia cell line U937 and normal human monocytes It was observed that
marmesin exhibited an IC50 value of 40 µM and exerted its cytotoxic effects in a dose-dependent manner. However, the cytotoxic effects of
marmesin were comparatively lower for the normal human monocytes as evident from the IC50 of 125 µM. Our results indicated that
marmesin inhibits colony formation and induces apoptosis dose-dependently. We also investigated the effect of
marmesin on the expression of Bax and Bcl-2
proteins. It was observed that
marmesin treatment triggered upregulation of Bax and downregulation of Bcl-2 causing significant increase in the Bax/Bcl-2 ratio,
marmesin could also induce ROS mediated alterations in mitochondrial membrane potential. Additionally,
marmesin induced G2/M cell cycle arrest and significantly inhibited cell migration potential of
leukemia cells at the IC50. Remarkably,
marmesin prevent
tumor growth significantly in vivo at the dosage of 30 mg/kg in vivo. These results strongly indicate that
marmesin may prove to be a novel anticancer lead for the management of
leukemia.