Potentiation of Photodynamic Therapy in bladder cells with the natural flavonoid sylibin

MAMONE L, GANDARA L, RODRIGUEZ L, SANDES E, EIJáN AM, DI VENOSA G, CASAS A, BATLLE A

Cardiff

Congreso; Porphyrins and Porphyrias 2011; 2011

Photodynamic therapy (PDT) is an anticancer treatment based on light-induced destruction of photosensitised malignant cells and tissues. In the last years, 5-aminolevulinic acid (ALA), a biochemical precursor of the potent photosensitiser protoporphyrin IX (PpIX), has been successfully used for fluorescent diagnosis and photodynamic treatment of cancer. PDT is an important treatment for bladder cancer due to the easy light access to the tumour via endoscopy. Sylibin a natural flavonoid, obtained from Silybum marianum, is currently used as a liver protector. In addition, our group has reported its antitumour properties per se as well as potentiation of the efficacy of several antitumour treatments. In the present work, we have evaluated the cytotoxicity of the combinated treatment, ALA-PDT and sylibin, in two bladder cancer cell lines: the human T24 and the murine MB49. The cells were exposed to luminic doses inducing 50% of cell death (LD50, expressed in Joules/cm2). After 19 h of ALA-PDT, the cytotoxicity was evaluated by the MTT method. The T24 cell line is more sensitive to ALA-PDT than the MB49 cell line, being the LD50; 0.025 J/cm2 for T24 and 0.05 J/cm2 for MB49. The combined treatment consists of ALA-PDT treatment with LD50 of cells pre-treated with sylibin 24h before. In the MB49 cells, sylibin 50 ìM and 30 ìM induces per se 37% and 24% cytotoxicity respectively, whereas the combination with ALA-PDT increases the cell death by 25% and 13%. Similar results were obtained for the T24 cell line, but this cell line is less sensitive to sylibin treatment. Since non toxic sylibin doses do not potentiate the PDT effect and the combinated treatment is not synergistic but additive, we conclude that the mechanism of action of both treatments are different. These results suggest that the combination of sylibin and ALA-PDT would increase PDT efficacy.