ENHANCEMENT OF PHOTODYNAMIC THERAPY IN GASTRIC-CANCER CELLS BY REMOVAL OF IRON

Background-Aminolaevulinic acid (ALA) is an endogenous substrate in th e haem biosynthetic pathway. Protoporphyrin IX (PPM), the immediate ha em precursor in the pathway, has photoexcitable properties. Exogenous ALA has been used previously as a precursor agent in photodynamic ther apy (PDT). Its main advantage is a short half-life and hence reduced i ncidence of skin photosensitivity. ALA can be toxic, however, causing, for example, transient increases in liver enzyme concentrations when given systemically and this may be dose related. Aim-To assess whether accumulation of PPM and ultimately the efficacy of PDT could be impro ved by modulating both ends of the haem biosynthetic pathway. Methods- Gastric cancer cells (MKN 28) were incubated with ALA (0-1000 mu molar ) and desferrioxamine (0-800 mu molar) for 24 hours before exposure to argonpumped dye laser (630 nm) at different energy levels (0-40 J/cm( 2)). Cell viability was assessed by use of the methyl-tetrazolium (MTT ) assay four hours after exposure to light. Results-Total PPM accumula tion increased linearly with increasing extracellular concentrations o f ALA up to 1 mmolar (r = 0.973, p < 0.005). Adding 200 molar of desfe rrioxamine trebled PPM accumulation over the same period of incubation . Cell viability after exposure to light decreased with low doses (0-3 0 mu molar) of desferrioxamine (r = -0.976, p = 0.024). However, highe r doses of desferrioxamine (more than 40 molar) seemed to confer a pro tective effect against PDT. Conclusion-PDT using ALA can be improved b y removal of available iron with desferrioxamine. The reason for the p rotective effect of desferrioxamine seen at higher doses is not clear.