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


OBJECTIVE
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.
Mu
Deguang
D
Department of Respiratory Disease, Tangdu Hospital, Fourth Military Medical University, 1# Xinsi Road, Xi'an city, Shaanxi Province, 710038, China.
Zhang
Wei
W
Chu
Dongling
D
Liu
Tonggang
T
Xie
Yonghong
Y
Fu
Enqing
E
Jin
Faguang
F
D000962:Antimalarials / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D000962:Antimalarials; D037621:Artemisinins; D002614:Chelating Agents; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; D011725:Pyridines; D012717:Sesquiterpenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C039060:artenimol; D048051:p38 Mitogen-Activated Protein Kinases; C022616:thiazolyl blue; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D002118:Calcium