The effect of quercetin on light-induced cytotoxicity of hypericin.

Protective effect of quercetin, a natural antioxidant compound, on hypericin-induced cytotoxicity was studied in human promyelocytic leukemia cells (HL-60). Hypericin (10(-5) mol x l(-1)) alone significantly decreased cell survival to 21% that found in the controls, whereas in combination with quercetin (10(-5) mol x l(-1)) this decrease was diminished to 46%. Lower concentrations of quercetin had no protective effect. These findings indicate that oxygen radicals can play an important role in hypericin-induced phototoxic effects.

Melatonin and retinyl acetate as chemopreventives in DMBA-induced mammary carcinogenesis in female Sprague-Dawley rats.

One goal of experimental oncology is to find and test effective chemopreventive substances which can suppress malignant transformation of the cells, their accumulation and invasion. Mammary gland tumours were induced by DMBA applied intragastrically (10 mg/rat, three times) every three days between postnatal days 50 and 60 in female Sprague-Dawley rats. One day after the last dose we started chemoprevention with Mel, RA and combination of both drugs, which lasted 25 weeks. Mel was drunk continuously as a solution in tap water (100 micrograms/ml). RA was applied daily in the dose of 8.2 mg/rat at the base of the tongue. There were four experimental groups: 1. control--no chemoprevention, 2. Mel treatment, 3. RA treatment, 4. application RA + Mel. At the end of the experiment the incidence, frequency, latency and average volume of tumours were evaluated. In the group treated with Mel tumour incidence, latency and volume did not differ from controls; the frequency of tumours was decreased. Treatment with RA and with combination RA + Mel decreased mammary tumour incidence to 38% (RA) and 48% (RA + Mel); it also decreased frequency and prolonged latency. Thus chemoprotective effects of RA and combination of RA with Mel were proved in mammary carcinogenesis induced by DMBA. The oncostatic effect of Mel alone was not confirmed. In our recent paper (Bojková et al., 2000) drinking of lower doses of Mel during the late afternoon and night prolonged the latency period and in combination with RA showed an oncostatic effect on mammary carcinogenesis induced by NMU. Further studies are needed to elucidate the conditions of successful chemoprevention with Mel.

Potentiation of hypericin and hypocrellin-induced phototoxicity by omeprazole.

Hypericin and hypocrellin are potential antiviral and antineoplastic agents with multiple modes of light-induced biological activity connected with a production of singlet oxygen and/or excited-state proton transfer and consequent pH drop formation in the drugs environment. In present work light-induced cytotoxicity of hypericin (1 x 10(-5) - 10(-9) mol) and hypocrellin (1 x 10(-5) - 10(-9) mol) and potentiating effect of omeprazole on human leukemic cell line HL-60 was studied. Under dark condition cultivation none cytotoxicity was observed. The only one exception was hypocrellin in concentration 1 x 10(-5) mol which displayed full cytotoxic effect. However, illumination increased cytotoxic effect of hypericin and hypocrellin, both. Omeprazole, an inhibitor of H+K+-ATPase, has been used for testing the hypothetical pH decreasing effect of hypericin and hypocrellin in their cytotoxic mechanism of action. The results of our experiments have shown that in HL-60 cell line the effect of hypericin and hypocrellin at 1 x 10(-6) mol (both) was significantly potentiated by omeprazole in concentrations 1 x 10(-6) - 10(-9) mol. Our results support the hypothesis that the excited-state proton transfer and the consequent acidification of hypericin and hypocrellin environment could play a role in the biological activity of both agents.