Photodynamic therapy using zinc phthalocyanine with low dose of diode laser combined with doxorubicin is a synergistic combination therapy for human SK-MEL-3 melanoma cells.

Chemotherapy is a generally used anticancer strategy for melanoma and it may have improved outcomes in combination with other approaches. One such strategy is photodynamic therapy (PDT), where a photosensitizer (PS) generates reactive oxygen species (ROS) after illumination of target cells. Interestingly, in low doses and high doses of light sources, special cellular responses can be induced. Regarding this fact, in this study, the combination of zinc phthalocyanine (ZnPc)-PDT and Doxorubicin (DOX) was applied at low and high dose of diode laser to treat SK-MEL-3 cells. Cytotoxic effects were determined by MTT assay for assessment synergistic effects were estimated by calculation of Combination Index (CI); that synergistic effects were observed in most groups. In low dose of laser irradiation higher synergism effects were observed. Significant changes of ROS were not observed with combinations, but autophagy, subG1 and G2/M phase cell cycle arrest, decreased cell migration ability and apoptosis induction were significantly increased compared to either treatment alone. The expression of caspase-8, -9, -3 and Bcl-2 genes revealed caspase-dependent apoptosis in all groups. Moreover, ZnPc-PDT and chemo-PDT down-regulated the expression of MMP-9 and Vimentin genes that impaired cell migration. In conclusion, it can be suggested that pre-treatment with ZnPc-PDT has high effects to sensitize SK-MEL-3 cells to DOX, in particular with low dose of diode laser.

The interaction between the light source dose and caspase-dependent and -independent apoptosis in human SK-MEL-3 skin cancer cells following photodynamic therapy with zinc phthalocyanine: A comparative study.

The aim of this study is to determine the behavior of relative expression of Bcl-2, caspase-8, caspase-9, and caspase-3 genes of/in SK-MEL-3 cancer cells and explore molecular mechanisms responsible for the apoptosis response during an in vitro photodynamic therapy (PDT) with Zinc Phthalocyanine (ZnPc) using different doses of the light source. In this study, firstly the cytotoxic effects of ZnPc-PDT on SK-MEL-3 cells were evaluated. By irradiating the laser, ZnPc induced a significant amount of apoptosis on SK-MEL-3 cells in three IC50s including 0.064±0.01, 0.043±0.01, and 0.036±0.01µg/mL at the doses of 8, 16, and 24J/cm2, respectively. Moreover, flow cytometry and QRT-PCR experiments were done. The high percentage of apoptotic cells was seen in the early apoptosis stage. The expression of Bcl-2 and caspase-8 genes at all doses of laser experienced an obvious reduction in comparison to the control group. On the other hand, although the expression of caspase-9 and caspase-3 genes remains almost constant at 8J/cm2, but they faced an increment at 16 and 24J/cm2 doses. These data reveal caspase-dependent apoptosis in high and caspase-independent apoptosis in low doses of laser. Based on the results of present work, it can be suggested that the dose of the light source is a key factor in induction of caspase-dependent and caspase-independent apoptosis pathways following PDT.