Endocavitary Therapy of Superficial Cancer Bladder: Evaluation of Photobiological Activity of Psoralen Derivatives on in Vitro Reconstituted Bladder Mucosa

Abstract

The development of high selectivity drugs for urothelial neoplasia is one of the goals in endocavitary therapy of superficial cancer bladder improvement. Photochemotherapy could cover an important role, because it enables to selectively treat the neoplastic lesions thanks to compounds sensitised by light sources specifically addressed. Aims of this study was to evaluate the in vitro biological activity on normal and neoplastic urothelium of a psoralen derivative, 4-Methyl-11-dimethilaminopropoxy-benzopsoralen (G50-E), against 8-methoxypsoralen (8-MOP) reference drug. Both of them are photosensitied by UVA radiations (photochemotherapy PUVA). An experimental model, which reproduces, even if in a simplified manner, the human bladder mucosa and submucosa organization, was in this study adopted. Firstly, we evaluated the antiproliferative activity of these psoralen derivatives on neoplastic and normal origin human urothelial cell lines. For this we determined the relative IC50 by means of cytotoxic test on cellular monolayer with Trypan Blue. In a second phase of this study, we took advantage from reconstitution technique of bladder mucosa proposed by Fujiyama and previously optimized by our group to evaluate on a three-dimensional model the IC50 effects due to both considered compound. Pharmacologically treated neo-bladder and the control ones were evaluated by means of scanning electron microscopy (SEM) observations. The meaningful result appeared in cellular monolayer experimentation was the selectivity exhibited by both tested compounds (particularly G50-E) against the neoplastic origin urothelial cells. Moreover, scanning electron microscopy investigation, carried on neo-bladder, confirmed the G50-E cytotoxic effect. Therefore, these results suggested the benefit of PUVA therapy for superficial bladder cancer. But, we have to remind that the microscopic observations are just a initial approach and further researches are necessary to quantify the functional and sub-microscopic damage on three-dimensional models.