Chlorin e6-C-15-ethyl ester (LS-HB), a newly identified photosensitizer, was isolated from chlorin e6. The mechanism of tumor cell death induced by photodynamic therapy with LS-HB (LS-HB-PDT) is still unknown. Here, we investigated the photophysical properties of LS-HB, evaluated the antitumor effect on melanoma in vitro and in vivo, and explored its possible mechanisms. LS-HB not only has an optimal spectral band of red wavelength (660 nm) for photosensitization but also has favorable photostability. More importantly, LS-HB-PDT elicited a potent dose-dependent phototoxic effect in vitro. We discovered that LS-HB located in the mitochondria of B16F10 cells was able to generate excess reactive oxygen species, which subsequently resulted in mitochondrial membrane potential loss and induced apoptosis via caspase-9 and caspase-3 pathways. Moreover, PDT with LS-HB markedly inhibited the growth of melanoma in vivo. Therefore, LS-HB is expected to be an effective potential photosensitizer in antitumor therapy.
Keywords: apoptosis; melanoma; mitochondria; photodynamic therapy; photosensitizers; reactive oxygen species (ROS).