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Involvement of Mitochondria–Caspase Pathway in Hemoporfin‐mediated Cell Death
Author(s) -
Wei Yongqing,
Kong Beihua,
Song Kun,
Qu Xun,
Jin Qiong,
Yang Qifeng
Publication year - 2007
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2007.00160.x
Subject(s) - mitochondrion , microbiology and biotechnology , caspase , programmed cell death , apoptosis , chemistry , cell , biology , biochemistry
Hemoporfin is a novel second‐generation porphyrin‐related photosensitizer for ovarian cancer photodynamic treatment (PDT). The purpose of this study was to investigate the molecular mechanisms of Hemoporfin‐mediated photocytotoxicity. Human epithelial ovarian cancer cell line 3AO was incubated with different concentrations of Hemoporfin, and phototoxic effects of Hemoporfin on cells were determined using a Cell Viability Analyzer. Apoptosis or necrosis was determined by flow cytometry analysis using the Annexin V‐FITC apoptosis kit. Cellular caspase activation was determined using the fluorescent assay kit for caspase‐3 and caspase‐9. Rhodamine123 was used as a mitochondrial probe and Lucifer Yellow as a lysosomal probe to investigate the intracellular localization of Hemoporfin in 3AO cancer cells. We demonstrated that both high‐dose (30 μg mL −1 ) and low‐dose (3 μg mL −1 ) Hemoporfin significantly reduced the viability of ovarian cancer cell 3AO with light illumination, and the photocytotoxicity was dose‐dependent ( P < 0.01). Using a mitochondrial fluorescence probe, we demonstrated a distinct mitochondrial aggregation in 3AO cells with a low concentration of Hemoporfin. Loss of mitochondrial membrane potential was detected as early as 1 h after Hemoporfin‐mediated PDT. PDT with low‐dose Hemoporfin predominantly induced apoptosis but not necrosis, and both caspase‐3 and caspase‐9 were activated. Based on our results, mitochondria play an important role in the Hemoporfin‐induced apoptosis, and mitochondria membrane potential loss initiated apoptosis via the activation of caspases. Understanding the mechanisms involved in PDT‐mediated apoptosis may improve its therapeutic efficacy and facilitate its transition into the clinic.