The role of calcium, P38 MAPK in dihydroartemisinin-induced apoptosis of lung cancer PC-14 cells

Abstract

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, is an effective novel antimalarial drug. Recent studies suggest that it also has anticancer effect. The present study was designed to investigate the effects of DHA on cultured human lung cancer cells (PC-14 cells) to better understand its apoptosis and apoptosis-related factors in vitro. The cell viability was measured by MTT assay. The apoptosis induction was examined by DNA ladder and flow cytometry. The intracellular-free calcium concentration in the lung cancer cells were evaluated by laser scanning confocal microscopy with Fura-3/AM as probe. The associated gene expression was examined by Western blot. After treatment with DHA, a decrease in the viability of PC-14 cells and apoptosis were observed. DHA-induced apoptosis were accompanied by an increase of Ca(2+) and activation of p38. Deleted levels of Ca(2+) by BAPTA-AM 20 microM or inhibition of p38 by its selective inhibitor SB202190 then led to decreased DHA-induced apoptosis. These results demonstrated that DHA can induce apoptosis of lung cancer cell line PC-14 cells and calcium and p38 play important roles in the apoptotic signalling pathways.