Increased Photosensitivity in HL60 Cells Expressing Wild‐Type p53

Abstract

Loss of p53 function has been correlated with decreased sensitivity to chemotherapy and radiation therapy in a variety of human tumors. Comparable analysis of p53 status with sensitivity to oxidative stress induced by photodynamic therapy has not been reported. In the current study we examined photosensitivity in human promyelocytic leukemia HL60 cells exhibiting either wild-type p53, mutated p53 or deleted p53 expression. Experiments were performed using a purpurin, tin ethyl etiopurpurin (SnET2)-, or a porphyrin, Photofrin (PH)-based photosensitizer. Total SnET2 accumulation was comparable in all three cell lines. Uptake of PH was highest in cells expressing wild-type p53 but incubation conditions could be adjusted to achieve equivalent cellular PH levels during experiments that analyzed photosensitivity. Survival measurements demonstrated that HL60 cells expressing wild-type p53 were more sensitive to PH- and SnET2-mediated photosensitization, as well as to UVC irradiation, when compared to HL60 cells exhibiting deleted or mutated p53 phenotypes. A rapid apoptotic response was observed following purpurin- and porphyrin-induced photosensitization in all cell lines. Results of this study indicate that photosensitivity is increased in HL60 cells expressing wild-type p53 and that photosensitizer-mediated oxidative stress can induce apoptosis through a p53-independent mechanism in HL60 cells.

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

“…Although PDT causes a direct activation of the ®nal stages of apoptosis (Kessel et al, 1997;Kessel and Luo, 1999;Oleinick and Evans, 1998), the sensitivity of cells to PDT can vary between closely related cell lines as a function of the expression of particular genes. Thus, HL60 cells expressing wild-type p53 were more sensitive to cell killing by PDT than were HL60 cells in which p53 genes were deleted or mutant, although all lines underwent a rapid apoptotic response (Fisher et al, 1997). Chinese hamster ovary cells expressing a human Bcl-2 gene were partially resistant to apoptosis and to overall cell death after PDT sensitized by the phthalocyanine Pc 4 (He et al, 1996).…”

Protoporphyrin IX Interacts with Wild-type p53 Protein in Vitro and Induces Cell Death of Human Colon Cancer Cells in a p53-dependent and -independent Manner

“…This may suggest that the sensitizers themselves, without laser excitation, can cause cancer cell death. Furthermore, the fact that human promyelocytic leukemia HL60 cells expressing wt-p53 were more sensitive to Photofrin/SnET2-mediated PDT than the HL60 cells expressing mutated or deleted p53 gene clearly indicates the relevance of wild-type p53 in the response of cancer cells to porphyrin-mediated PDT (23).…”

Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo

“…The process of apoptosis has become central to the understanding of the development of normal tissues, the carcinogenic process and the response of tumours to anticancer agents (Berry et al, 1990;Meterissian, 1990;Lowe et al, 1994;Luo et al, 1996;Fisher et al, 1997;Thatte and Dahanikar, 1997). Currently, methods for detecting and monitoring this process are invasive and timeconsuming.…”