Opposite effects of nanocrystalline fullerene (C60) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C60

In the present study, we compared the effects of nanocrystalline fullerene suspension (nanoC60) on tumour cell growth in vitro and in vivo. NanoC60 suspension was prepared by solvent exchange using tetrahydrofuran to dissolve C60. In vitro, nanoC60 caused oxidative stress, mitochondrial depolarization and caspase activation, leading to apoptotic and necrotic death in mouse B16 melanoma cells. Biodistribution studies demonstrated that intraperitoneally injected radiolabeled (125I) nanoC60 readily accumulated in the tumour tissue of mice subcutaneously inoculated with B16 cells. However, intraperitoneal administration of nanoC60 over the course of two weeks starting from melanoma cell implantation not only failed to reduce, but significantly augmented tumour growth. The tumour-promoting effect of nanoC60 was accompanied by a significant increase in splenocyte production of the immunoregulatory free radical nitric oxide (NO), as well as by a reduction in splenocyte proliferative responses to T- and B-cell mitogens ConcanavalinA and bacterial lipopolysaccharide, respectively. A negative correlation between NO production and splenocyte proliferation indicated a possible role of NO in reducing the proliferation of splenocytes from nanoC60-injected mice. These data demonstrate that nanoC60, in contrast to its potent anticancer activity in vitro, can potentiate tumour growth in vivo, possibly by causing NO-dependent suppression of anticancer immune response.