Ferrochelatase, a novel target for photodynamic therapy of cancer

This study was designed to investigate the hypothesis that the inhibition o f ferrochelatase will cause ill situ build up of high concentrations of pro toporphyrin-IX which may act as a putative agent for photodestruction of ca ncer cells. The parenteral administration of lead acetate, a known inhibito r of ferrochelatase, to mice bearing cutaneous tumors (papillomas and carci nomas) caused a six-fold enhancement in the concentration of protoporphyrin -IX in tumors within a period of one month. Forty-eight hours after the sec ond injection of lead, mice were exposed to visible light, at a light dose of about nine kilo lux for a period of one hour tin four sittings of fiftee n minutes each keeping a gap of ten minutes between two exposures). A signi ficant reduction in tumor size was observed starting as early as day one fo llowing the treatment. Continuous treatment for six consecutive days result ed in almost complete ablation of the tumor mass in most of the animals. Co mplete regression of the tumors was observed at two to three days following the first exposure. Our observations on iii situ accumulation of protoporp hyrin-IX by heme-biosynthesis inhibition represent a novel method for photo dynamic 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.