Title

 

Authors

M. Lenzi¹, C. Fimognari¹, L. Ferruzzi¹,  E. Turrini¹, G. Cantelli-Forti¹, P. Hrelia¹

Dept. of Pharmacology, Alma Mater Studiorum Università di Bologna

 

Abstract

For decades, plant-derived natural products have been useful for the development of antitumor therapies in modern medicine. We evaluated the anticancer effect of a traditionally-used plant, Hemidesmus indicus, and subsequently tried to elucidate its mechanism of actions in T-leukemia cells by flow cytometry. By this way, we demonstrated that Hemidesmus is able to affect critical points of the cell cycle via modulation of the expression of cyclin E, cyclin-dependent kinase 2, and p21. Moreover, it induced apoptosis at all the concentrations tested mediated by a loss of mitochondrial transmembrane potentialand increased Bax/Bcl-2 ratio. ADP, adenine nucleotide translocator and mitochondrial permeability transition pore inhibitors did not reverse Hemidesmus-induced mitochondrial depolarization. Hemidesmus induced a significant [Ca²⁺]_i raise through the mobilization of intracellular Ca²⁺ stores. Overall, these results indicate the molecular basis of the antileukemic effects of Hemidesmus and identify the mitochondrial pathways and [Ca²⁺]_i as crucial actors in Hemidesmus-induced anticancer activity.