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 therapy (PDT)-induced cell death, we introduced a wild-type p53 gene into the HT29 colorectal carcinoma cell line, which bears an endogenous mutant p53, using a lipofectin system. The influence of p53 status on the sensitivity induced by 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitization 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 microM 2-BA-2-DMHA with a red light of 18 J/cm2 (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 following PDT appears earlier in HT29 cells infected with wild-type p53 than in parent HT29 cells and empty vector-infected HT29 cells. These findings suggest that although wild-type p53 is, by itself, insufficient to induce apoptosis in cells with p53 mutation, it enhances the photosensitivity of 2-BA-2-DMHA by strongly potentiating the induction of apoptosis.
Zhang
W G
WG
Institute of Biophysics, Academia Sinica, Beijing, People's Republic of China.
Li
X W
XW
Ma
L P
LP
Wang
S W
SW
Yang
H Y
HY
Zhang
Z Y
ZY
D017209:Apoptosis; D016193:G1 Phase; D019073:HT29 Cells; D006801:Humans; D009154:Mutation; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C114700:2-butylamino-2-demethoxy-hypocrellin A; D017319:Photosensitizing Agents; D011809:Quinones; D016159:Tumor Suppressor Protein p53; D010569:Perylene