Ferrochelatase, a novel target for photodynamic therapy of cancer

This study was designed to investigate the hypothesis that the inhibition of ferrochelatase will cause in situ build up of high concentrations of protoporphyrin-IX which may act as a putative agent for photodestruction of cancer cells. The parenteral administration of lead acetate, a known inhibitor of ferrochelatase, to mice bearing cutaneous tumors (papillomas and carcinomas) caused a six-fold enhancement in the concentration of protoporphyrin-IX in tumors within a period of one month. Forty-eight hours after the second injection of lead, mice were exposed to visible light, at a light dose of about nine kilo lux for a period of one hour (in four sittings of fifteen minutes each keeping a gap of ten minutes between two exposures). A significant reduction in tumor size was observed starting as early as day one following the treatment. Continuous treatment for six consecutive days resulted in almost complete ablation of the tumor mass in most of the animals. Complete regression of the tumors was observed at two to three days following the first exposure. Our observations on in situ accumulation of protoporphyrin-IX by heme-biosynthesis inhibition represent a novel method for photodynamic therapy of cancer cells. It is important to emphasize that lead is a fairly toxic agent and developing a non-toxic agent is one of our future goals.