Dietary vitamin D supplementation does not reduce the incidence or severity of asbestos-induced mesothelioma in a mouse model.

Epidemiological studies suggest that vitamin and mineral intake is associated with cancer incidence. A prevention strategy based on diet or dietary supplementation could have enormous benefit, both directly, by preventing disease, and indirectly by alleviating fear in millions of people worldwide who have been exposed to asbestos. We have previously shown that dietary supplementation with the antioxidants vitamins A, E, and selenium does not affect overall survival nor the time to progression of asbestos-induced mesothelioma in MexTAg mice. Here we have extended our analysis to vitamin D. We compared survival of asbestos-exposed MexTAg mice provided with diets that were deficient or supplemented with 4500 IU/kg vitamin D (cholecalciferol). Survival of supplemented mice was significantly shorter than mice given a standard AIN93 diet containing 1000 IU/kg cholecalciferol (median survival was 29 and 32.5 weeks respectively). However, mice deficient in vitamin D had the same rate of mesothelioma development as control mice. Neither the latency time from asbestos exposure to diagnosis nor disease progression after diagnosis were significantly different between mice on these diets. We conclude that vitamin D is unlikely to moderate the incidence of disease in asbestos-exposed populations or to ameliorate the pathology in patients with established mesothelioma.

The antioxidants vitamins A and E and selenium do not reduce the incidence of asbestos-induced disease in a mouse model of mesothelioma.

Epidemiological evidence indicates that supplementation with some dietary factors is associated with a lower incidence of cancer. An effective cancer prevention strategy for the millions of people worldwide who have been exposed to asbestos could have enormous benefit. We tested whether dietary supplementation of the antioxidants vitamin A, E, and selenium could alter the pattern of disease in the MexTAg transgenic mouse model, in which mice uniformly develop mesothelioma after asbestos exposure. We focused on antioxidants because one of the most widely accepted hypotheses for the mechanism by which asbestos fibers cause cancer proposes the involvement of reactive oxygen and nitrogen species. We compared the survival of MexTAg mice that had been inoculated with asbestos fed on diets supplemented with 250,000 IU/kg vitamin A (retinoic acid), or 1,000 mg/kg vitamin E (α-tocopherol acetate) or 3 mg/kg selenium, or both vitamin E and selenium concurrently and, additionally, diets deficient in each antioxidant. We found that neither the time to develop symptoms of disease nor overall survival times were altered by any of the diets. We conclude that the data do not support the notion that dietary antioxidants will moderate the rate of mesothelioma in asbestos-exposed populations.

Antitumor efficacy of the novel chemotherapeutic agent coramsine is potentiated by cotreatment with CpG-containing oligodeoxynucleotides.

Coramsine is a novel chemotherapeutic agent isolated from Solanum linnaeanum (devil's apple). Topical treatment provides clinical benefit for skin tumors. To evaluate the potential broader applicability of the drug, its in vivo anticancer efficacy in a murine model of malignant mesothelioma and its mode of action were investigated. Systemic administration of coramsine slowed tumor growth and prolonged survival time. Importantly, the antitumor efficacy of coramsine was enhanced when treatment was combined with stimulation of innate immunity using unmethylated CpG-containing oligodeoxynucleotides (ODNs). Combination treatment further slowed tumor growth and provided a survival benefit. Coramsine seems to kill tumor cells by direct cell lysis. Using 2 different assays to detect apoptosis (caspase activation and DNA fragmentation), we found no evidence that coramsine induces any form of programmed cell death. The fact that the efficacy of coramsine is potentiated by CpG ODNs suggests that coramsine-induced cell death is an immunologic null event.