In Vitro Biological Effects Of Novel Type 1 Photosensitizers And Their Mechanism Of Action

Photodynamic therapy involving Type 2 photosenstizers has been conspicuously successful in the treatment of various lesions. Type 1 process, in contrast has not received much attention despite its considerable potential. We have prepared several classes of molecules containing fragile bonds that will produce reactive intermediates such as radicals and nitrenes upon photoexcitation with UV-A and visible light. In a primary screen, many of these compounds had a significant concentration and light dose dependent effect on the cell viability on U937. The chemistry of these compounds differentiated their ability to induced cytotoxic effects. To further establish these findings, we tested one compound representing each class of chemistry in three different tumor cell lines. Cells were incubated with three different concentrations (100 mu M, 25 mu M and 6.25 mu M) and exposed to UV light dose of 4J/cm(2) and 8J/cm(2). The compounds showed varying effects on viability in different cell lines. Finally we also investigated the ability to induce apoptosis as the mechanism of cell death in HCT116 cell lines using the experimental conditions mentioned. The type 1 photosensitizers induced apoptosis as early as 4 hours after exposure in HCT116 cells and the rate of apoptosis increased with time with majority of cells in late apoptotic or necrotic stage.