Photoactivation of hypericin is known to generate singlet oxygen and superoxide anion radicals. Reactive oxygen species (ROS) produced by photodynamic therapy (PDT) has the capacity to induce oxidative damage and tumor destruction. We have previously shown that hypericin-PDT induces tumor shrinkage and regression in the human nasopharyngeal cancer (NPC)/HK1 murine tumor model. In this extended study, we show by electron microscopy that subcutaneously implanted HK1 NPC cells from Balb/c nude mice perished by cell necrosis with hypericin-PDT treatment. There was evidence of cytoplasmic swelling accompanied by loss of cell membrane integrity and autophagic vacuolization of cytoplasm but no nuclear changes. There was also no significant difference in the apoptotic index of control and PDT-treated tumors, when analyzed by in situ end labeling of DNA strand breakage to detect apoptosis. This further supports the observation that cell death in PDT-treated NPC/HK1 tumors was by necrosis. Lipid peroxidative stress analyzed by the malonaldehyde assay was significantly elevated in PDT-treated cells. However, PDT had no effect on the activity of superoxide dismutase, an intracellular antioxidant enzyme. The findings show that hypericin-PDT of nasopharyngeal tumors in vivo induces tumor necrosis with accompanying lipid peroxidation.

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