APOPTOTIC POTENTIAL OF NEW AMPHIPHILIC CHLORINE AS A PHOTOSENSITIZER FOR PHOTODYNAMIC THERAPY

Abstract

Photodynamic therapy (PDT) is a strategy used to treat various types of tumors in that light stimulates a photosensitizer (PS) to generate reactive oxygen species (ROS) that lead to cell death by apoptosis or necrosis. In an attempt to increase the solubility of PS chlorine (CHL), the Trisma group was added (CHL-TRISMA) in order to reduce aggregation in aqueous solution which impairs its use in PDT. Several parameters (light dose, type of PS, PS incubation time) can trigger different apoptotic pathways. In the literature there are several suggestions related to apoptosis pathways induced by in vitro PDT with hypericin. However, few studies on this subject have been conducted with chlorines. Thus, the objective of this project is to characterize molecular and cytotoxic effects of a synthesized chlorin and elucidate the pathways related to apoptosis triggered by PDT with CHL-Trisma. The main hypothesis of this work is that it has modified chlorin greater efficiency in the induction of apoptosis. To test this hypothesis, it will be evaluated the induction of apoptosis by intrinsic and extrinsic pathways, the generation of ROS, and in the protein level we will evaluate the expression of some proteins of MAPKs pathway by Western blot. Thus, it is expected to clarify the cellular and molecular mechanisms involved in cell death induced by PDT.