Hypocrellins and Hypericin induced apoptosis in human tumor cells: A possible role of hydrogen peroxide
We examined whether generation of H2O2 is a critical event for the apoptotic pathway upstream of mitochondrial involvement and caspase-3 protease activation. Perylquinone photosensitizers such as Hypocrellin A (HA), Hypocrellin B (HB) and Hypericin (HY) induced activation of caspase-3 and apoptosis upon photoactivation. Generation of H2O2 was commonly detected after photoactivation within an hour, and scavenging of H2O2 caused cells to fail to undergo apoptosis. Flow cytometry demonstrated that H2O2 production preceded loss of mitochondrial membrane potential (ΔΨm) in photoactivated cells treated with HA, HB and HY. Then caspase-3 activity was activated, followed by DNA fragmentation. These findings suggest that HA, HB and HY upon photoactivation induce H2O2 generation, which causes (ΔΨm) and subsequently caspase-3 activation, resulting in apoptosis. These findings suggest that generation of H2O2 by photoactivation of HA, HB and HY causes activation of caspase-3. Therefore, H2O2 may function as a common mediator for apoptosis induced by HA, HB and HY. The present study also demonstrated that upon photoactivation HA, HB and HY induced a decrease in intracellular acidification, glutathione (GSH) depletion and an array of mitochondrial damage together with apoptotic morphological changes in the irradiated cells.
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Document Type: Research Article
Affiliations: Department of Medical Sciences, National Cancer Centre, School of Science, Singapore
Publication date: January 1, 2002
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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