Cytoprotective role of nitric oxide in HepG2 cell apoptosis induced by hypocrellin B photodynamic treatment.
Hypocrellin B (HB), a natural perylenequinone pigment, has been successfully employed in the photodynamic therapy (PDT) in a variety of human cancer cells due to its high singlet oxygen yield. To investigate the generation of nitric oxide (NO) and its role on cancer cell death induced by PDT, we used human hepatocellular carcinoma (HepG2) cells and HB as a photosensitizer. HB/light treatment decreased the growth of HepG2 cells in a dose-dependent manner with an IC50 of 3.10μM, activated caspase-3, -9 and induced apoptosis in HepG2 cells. It was found that exposure of the cells to HB/light resulted in inducible nitric oxide synthase (iNOS) activation and followed by significant increase in NO generation. Incubating cells with a NOS inhibitor N(ω)-monomethyl-l-arginine (l-NMMA) and an NO scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) enhanced HB/light-induced caspase-3, -9 activation and apoptosis significantly while decreasing DAF fluorescence-assessed NO generation substantially. Cells could be rescued from HB/light-induced apoptosis by an exogenous NO donor, sodium nitroprusside (SNP). Our findings suggested that induced NO was acting cytoprotectively and PDT efficacy of HB could be improved by using pharmacological modulators of NO or NOS.
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Yuan Yuan
YY
Ji
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Yan Jun
YJ
Ma
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: jwwang@suda.edu.cn.
Jian Wen
JW
Wang
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019610:Cytoprotection / Q000187:drug effects* / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D017319:Photosensitizing Agents; D011809:Quinones; D009569:Nitric Oxide; D010569:Perylene; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C064522:hypocrellin B
Apoptosis; HepG2 cells; Hypocrellin B; Nitric oxide; Photodynamic therapy