Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation

Abstract

Hypericin (Hyp) is traditionally used as an antidepressant and antiviral agent. It selectively accumulates in spheroids and is also used as a photosensitizer in the photodynamic therapy of cancer. The present study aimed to investigate the cytotoxic effect of Hyp-mediated photodynamic therapy (Hyp-PDT) on cell growth and apoptosis of K562 leukemia cells, and to examine the underlying mechanisms. Hyp-PDT was performed with different light intensities (0.1, 0.3 and 0.5 mW/cm2), different concentrations of Hyp (0, 0.2, 0.4 and 0.8 μg/ml) and different durations of irradiation (0, 2, 4 and 8 min) in order to select the optimal conditions for subsequent experiments. A concentration of 0.4 μg/ml Hyp with a 5 h drug-light interval and 4 min irradiation at 0.3 mW/cm2 light intensity was selected as the optimal conditions. The effects of Hyp-PDT on apoptosis were determined by detecting morphological changes under microscopy and by performing western blot analysis. The results revealed that Hyp-PDT suppressed cell viability in a light intensity-, dose- and irradiation duration-dependent manner. The expression levels of cleaved caspase-9, cleaved caspase-3 and phosphorylated-C-Jun N terminal kinase (JNK)l were significantly upregulated following Hyp-PDT. These results indicated that Hyp-PDT decreased cell viability and induced mitochondria-caspase-dependent apoptosis in the K562 cells through regulation of the JNK pathway. These findings suggest that Hyp-PDT may be developed as an effective treatment for leukemia.