The development of novel therapeutic agents to modulate programmed cell death independent of genetic background or malignant potential is a primary goal of modern
cancer therapy. In this report, the light activation- and concentration-dependent cytotoxicity of
calphostin C, a photoactivatable
perylenequinone, is carefully evaluated using a series of nine well-characterized human and rodent
prostate cancer cell lines representing the spectrum of
disease progression (e.g., variations in metastatic ability, ploidy, and tumor suppressor gene status). Treatment of these
cancer cell lines with nanomolar concentrations of
calphostin C in combination with increasing amounts of light exposure established a relationship between light and dose dependence of
calphostin C cytotoxicity. The induction of apoptosis is rapid, as evidenced by the fact that immediately
after treatment, cells exposed to
calphostin C with light activation exhibit both morphological and biochemical changes consistent with apoptosis (cellular and nuclear shrinkage and
chromatin condensation). For example, 78% of cells treated with 100 nM
calphostin C in combination with 2 h of light activation underwent apoptosis within 24 h of treatment.
DNA ladder formation could be detected within 12 h of treatment. In the absence of light activation, treatment with
calphostin C at all concentrations tested had no acute or durable cytotoxic effects in any of the cell lines. Our findings demonstrate that
calphostin C cytotoxicity is strictly light dependent. Furthermore, its efficacy is independent of the genetic background, p53 status, or in vivo malignant potential of a cell, making it a suitable candidate for the treatment of heterogeneous
tumor cell populations.