| Abstract [eng] |
Photodynamic therapy (PDT) is a treatment modality for the precancerous lesions of the skin and skin cancer. The effects of PDT on cancer cells have already been thoroughly studied. However, healthy cells surrounding the tumor are also affected during the PDT. In this work, the effect of PDT on human primary keratinocytes HEKa was investigated through their exposure to various localized photosensitizers: aluminum phthalocyanine disulfonate (AlPcS2a), which accumulates to lysosomal membranes, aluminum phthalocyanine tetrasulfonate (AlPcS4), which concentrates in the lumen of lysosomes, and m-tetra(3-hydroxyphenyl)-chlorin (mTHPC), which diffusely localizes to cellular membranes. We have demonstrated that PDT effects, mediated by AlPcS2a and AlPcS4, induce primary keratinocyte differentiation and apoptosis, while PDT effects, mediated by mTHPC, induce apoptosis and autophagy. We have also evaluated the effect of AlPcS2a-PDT on human epidermoid carcinoma A-431 cancer cells. We found that apoptosis is initiated, and the number of autophagosomes increases after lysosomal membrane photodamage. However, the final stages of autophagy do not occur. In response to PDT, not only cell death can occur. Also, the expression of pro-inflammatory and proangiogenic cytokines, followed by tumor development, can increase. After the exposure of A-431cells to PDT, we have established the increase of interleukin 1 α (IL-1α) and vascular endothelial growth factor A (VEGF-A) expression. It should be noted that the expression of these cytokines in primary keratinocytes remained unchanged. We have demonstrated that IL-1α stimulates VEGF-A expression after mTHPC-mediated PDT in human epidermoid carcinoma A-431 cells. |
