Dihydroartemisinine Enhances Dictamnine-induced Apoptosis via a Caspase Dependent Pathway in Human Lung Adenocarcinoma A549 Cells

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells anddihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report exploresthe molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosisin human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death.FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at highconcentration in which loss of mitochondrial membrane potential (ΔΨm) was not involved. In addition, inhibitionof caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying thatDic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increasedthe apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantlyattenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHAco-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentrationand cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhancedDic induced A549 cell apoptosis via a caspase-dependent pathway.