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 rigorously tested in vivo in tumor models. In this study LNCaP, PC-3 and DU-145 cells were used to test the cytotoxic effects of HYP in vitro, precursory to an in vivo study designed to investigate the effects of HYP in an established murine model for prostate cancer. Specifically, the model used employs immunocompromised nude mice bearing the LNCaP solid tumor xenograft. In vitro cytotoxicity experiments indicated that the dose causing 50% lethality for HYP in LNCaP, PC-3 and DU-145 cells were 2.07, 2.15 and 2.23 microM, respectively, following irradiation with red light (590 nm) for 30 min at a fluence rate of 0.1 J/cm2/s. Cells treated with HYP in the absence of photoirradiation showed no signs of cytotoxicity. A tissue distribution study was 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, tumor tissue eliminated HYP at a slower rate than any of the other tissues examined. Interestingly, HYP levels were maintained in serum 24 h after oral administration (5 mg/kg dose). A pilot study designed to examine the efficacy of HYP treatment in nude mice bearing LNCaP tumors conducted over 28 days suggested that HYP, in combination with photoirradiation, inhibits both tumor growth and the elevation of prostate-specific antigen levels. Although the results reported for the current studies are preliminary they do provide evidence for an application of HYP PDT to prostate cancer which warrants further investigation.
Xie
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Department of Surgery, Prostate Centre at Vancouver General Hospital, University of British Columbia, Vancouver, Canada.
Hudson
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JB
Guns
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ES
D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000873:Anthracenes; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin