Role of p38 MAPKs in hypericin photodynamic therapy-induced apoptosis of nasopharyngeal carcinoma cells.
The present study aims to determine the role of mitogen-activated protein kinases (MAPKs) in hypericin-mediated photodynamic therapy (HY-PDT)-induced apoptosis of the HK-1 nasopharyngeal carcinoma (NPC) cells. HY-PDT was found to induce proteolytic cleavage of procaspase-9 and -3 in HK-1 cells. Apoptotic nuclei were observed at 6 h after PDT whereas B-cell leukemia/lymphoma-2-associated-X-protein (Bax) translocation and formation of Bax channel is responsible for the cell death. Increase in phosphorylation of p38 MAPKs and c-Jun N-terminal kinase 1/2 (JNK1/2) was detected at 15-30 min after HY-PDT. The appearance of phosphorylated form of p38 MAPKs and JNK1/2 was inhibited by the singlet oxygen scavenger l-histidine. HY-PDT-induced cell death was enhanced by the chemical inhibitors for p38 MAPKs (SB202190 and SB203580), but not by the JNKs inhibitor SP600125. Knockdown of the p38alpha and p38beta MAPK isoforms by small interfering RNA (siRNA) are more effective than the p38delta in enhancing PDT-induced cell death. Augmentation of apoptosis by p38alpha or p38beta knockdown is also correlated with the increased proteolytic cleavage of procaspase-9 after HY-PDT treatment. Our results suggested that HY-PDT activated p38 MAPKs through the production of singlet oxygen. Inhibition of p38 MAPKs with chemical inhibitors or siRNA enhances HY-PDT-induced apoptosis of the HK-1 NPC cells.
Chan
Pui S
PS
Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
Koon
Ho K
HK
Wu
Zhen G
ZG
Wong
Ricky N S
RN
Lung
Maria L
ML
Chang
Chi K
CK
Mak
Nai K
NK
D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D045744:Cell Line, Tumor; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000873:Anthracenes; D034741:RNA, Small Interfering; D010569:Perylene; C004965:hypericin; D048051:p38 Mitogen-Activated Protein Kinases