INTRODUCTION: 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. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: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. PURPOSE: The present study was designed to investigate the effects of DHA on cultured humanlung cancer cells (PC-14 cells) to better understand its apoptosis and apoptosis-related factors in vitro. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Juan A Orellana; Diego E Hernández; Pascal Ezan; Victoria Velarde; Michael V L Bennett; Christian Giaume; Juan C Sáez Journal: Glia Date: 2010-02 Impact factor: 7.452