Mitochondrial reactive oxygen species and nitric oxide-mediated cancer cell apoptosis in 2-butylamino-2-demethoxyhypocrellin B photodynamic treatment.
Photodynamic therapy (PDT) is a novel and promising cancer treatment which employs a combination of a photosensitizing chemical and visible light to induce apoptosis in cancer cells. Singlet oxygen has been recognized as the main origin of oxidative stress in PDT. However, the precise mechanism of PDT-induced apoptosis is not well characterized, especially the dualistic role of nitric oxide (NO). To dissect the apoptosis pathways triggered by PDT, the intracellular free radicals in MCF-7 cells were investigated by examining a novel photosensitizer 2-butylamino-2-demethoxyhypocrellin B (2-BA-2-DMHB)-mediated PDT. It was found that exposure of the cells to 2-BA-2-DMHB and irradiation resulted in a significant increase of intracellular ROS in minutes, and then followed by cytoplasmic free calcium enhancement, mitochondrial nitric oxide synthase (mtNOS) activation, cytochrome c release, and apoptotic death. Scavengers of singlet oxygen or NO could attenuate PDT-induced cell viability loss, nucleus morphology changes, cytochrome c release, mitochondria swelling, and apo-apoptosis gene p53 and p21 mRNA levels. The results suggested that both ROS and NO played important roles in the apoptosis-induced by PDT.
Lu
Zhongbing
Z
State Key Laboratory of Brain and Recognition Laboratory, Institute of Biophysics, The Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
Tao
Yi
Y
Zhou
Zhixiang
Z
Zhang
Junjing
J
Li
Cong
C
Ou
Lingcheng
L
Zhao
Baolu
B
D017209:Apoptosis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000648:ultrastructure; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003497:Cyclic N-Oxides / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D010569:Perylene / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011809:Quinones / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D019810:Sodium Azide / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C437043:2-butylamino-2-demethoxy-hypocrellin B; D003497:Cyclic N-Oxides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007093:Imidazoles; D017319:Photosensitizing Agents; D011809:Quinones; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D010569:Perylene; D045304:Cytochromes c; D019810:Sodium Azide; D002118:Calcium