Wild-type p53 protein potentiates phototoxicity of 2-BA-2-DMHA in HT29 cells expressing endogenous mutant p53

To better understand the effects of p53 on the process of photodynamic ther apy (PDT)-induced cell death, we introduced a wild-type p53 gene into the H T29 colorectal carcinoma cell line, which bears an endogenous mutant p53, u sing a lipofectin system. The influence of p53 status on the sensitivity in duced by 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitiz ation was then examined. The results indicate that infection with wild-type p53 induces a growth arrest but does not induce cell death, and sensitizes the cells to PDT. At a concentration of 5 mu M 2-BA-2-DMHA with a red ligh t of 18 J/cm(2) (lambda = 600-700 nm), the survival is reduced from 58.72% in HT29 cells to 13.49% in wild-type p53-infected HT29 cells. Apoptosis fol lowing PDT appears earlier in HT29 cells infected with wild-type p53 than i n parent HT29 cells and empty vector-infected HT29 cells. These findings su ggest that although wild-type p53 is, by itself, insufficient to induce apo ptosis in cells with p53 mutation, it enhances the photosensitivity of 2-BA -2-DMHA by strongly potentiating the induction of apoptosis. (C) 1999 Elsev ier Science Ireland Ltd. All rights reserved.