Growth Inhibition and Apoptosis Inducing Effects of Artemisia absinthium L. Fractions on Chronic Myeloid Leukemia (K562) Cells

Abstract

Plant-derived active principles may serve as potent and cost effective alternative medicinal strategy for human ailments. Artemisia absinthium is a potent medicinal plant growing wild in Kashmir Himalayan region and used traditionally for several ailments. The objective of present study was to evaluate the cytotoxic effects of Artemisia absinthium extracts on Chronic myeloid leukemia cells (K562) followed by bioassay-guided fractionation and evaluation of cell death mechanism. Two potent fractions (AAH-7) and (AAM-5) were obtained which inhibited the cells exhibiting IC 50 values of 20.95 ± 2.60 μg/ml and 15.30 ± 1.24 μg/ml respectively and were comparatively less lethal to normal cells. The fractions led to chromatin condensation and DNA fragmentation in cells suggesting apoptosis. The fractions also led to an enhancement of intracellular reactive oxygen species (ROS) and diminution of mitochondrial membrane potential (MMP) leading to apoptosis. Flow cytometric analysis revealed the modulation of the cell cycle pattern and phosphatidylserine externalization. Treatment with fractions led to cleavage of Caspase-3, Poly ADP-ribose polymerase (PARP), decrease in the expression of Bcl-2 protein (anti-apoptotic) and an increase in expression of Bax protein (pro-apoptotic). The main constituents detected by GC-MS and LC-ESI-MS mainly included terpenoids which are fragrance producing components of Artemisia species.