Tumor-specific and Photodependent Cytotoxicity of Hypericin in the Human LNCaP Prostate Tumor Model

Abstract

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.

Hypericin‐induced Photocytotoxicity is Connected with G2/M Arrest in HT‐29 and S‐Phase Arrest in U937 Cells

“…From the above-mentioned data it follows that photoactivated hypericin induced differences between the two cell types in all tested parameters. This is in agreement with the findings of several studies focusing on the importance of photodynamic protocol, including photosensitizer concentration and cell line in cell response to photodynamic treatment (8,15,16), and also the crucial role of the histological origin of tumors in hypericin antitumor activity (53).…”

Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green

“…They generally, but not exclusively, involve certain natural and synthetic chemicals, pigments, dyes, or fluorophores such as porphyrins, hypericin, Evans blue, and Congo red, and function as diagnostic contrast materials for MRI, nuclear scintigraphy, or optical imaging to determine tissue viability, or even as therapeutics or theranostics 15 . Many of these compounds (e.g., porphyrin and hypericin derivatives) were initially developed as “tumour-specific” agents, but were subsequently discovered to be specifically necrosis-avid 43 44 . Therefore, it is not surprising for ICG to emerge as another necrosis-avid agent.…”

Selective enrichment of hypericin in malignant glioma: Pioneering in vivo results

“…However, other in vivo investigations using different subcutaneously implanted tumor cell lines in mice found maximum hypericin accumulation at 4-6 h after intravenous injection (32,36,37). In addition, maximum hypericin accumulation in subcutaneously implanted prostate cancer cells (LnCaP) was found at 1-2 h after oral administration of 5 mg/kg hypericin (38). Tissue distribution of hypericin was studied in Fischer rats bearing subcutaneously inoculated Ay-27 cells (rat bladder transitional cell carcinoma) after intravenous administration (1 and 5 mg/kg body weight).…”