Tumor-specific and photodependent cytotoxicity of hypericin in the human LNCaP prostate tumor model

Hypericin (HYP) has been reported to have photodependent cytotoxic activity in a variety of cancer cell lines. However, this activity has yet to be ri gorously tested in vivo in tumor models. In this study LNCaP, PC-3 and DU-1 45 cells were used to test the cytotoxic effects of HYP in vitro, precursor y to an in vivo study designed to investigate the effects of HYP in an esta blished murine model for prostate cancer. Specifically, the model used empl oys immunocompromised nude mice bearing the LNCaP solid tumor xenograft. In vitro cytotoxicity experiments indicated that the dose causing 50% lethali ty for HYP in LNCaP, PC-3 and DU-145 cells were 2.07, 2.15 and 2.23 muM, re spectively, following irradiation with red light (590 nm) for 30 min at a f luence rate of 0.1 J/cm(2)/s. Cells treated with HYP in the absence of phot oirradiation showed no signs of cytotoxicity. A tissue distribution study w as also carried out using the LNCaP solid tumor model to determine whether or not HYP is distributed to the target tissue. HYP was broadly distributed in tissues studied, including LNCaP tumor xenograft tissue. Furthermore, t umor tissue eliminated HYP at a slower rate than any of the other tissues e xamined. Interestingly, HYP levels were maintained in serum 24 h after oral administration (5 mg/kg dose). A pilot study designed to examine the effic acy of HYP treatment in nude mice bearing LNCaP tumors conducted over 28 da ys suggested that HYP, in combination with photoirradiation, inhibits both tumor growth and the elevation of prostate-specific antigen levels. Althoug h the results reported for the current studies are preliminary they do prov ide evidence for an application of HYP PDT to prostate cancer which warrant s further investigation.