Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma

Abstract

Antioxidant and anticancer properties of fullerene C60 and especially of its polyhydroxylated, water soluble derivatives (fullerols) make them appealing for biomedical applications. In order to analyse antitumor effects of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC)1, second generation of fullerol, melanoma cells of different intracellular features and invasive potential (B16, B16-F10, A375) were treated with 3HFWC in various concentrations (0.19-100 μg/ml) for 24, 48 and 72h. Subsequently, syngeneic murine melanoma model was used (oral 3HFWC intake, 0.15 g/l). The most prominent effect of 3HFWC, both in vitro and in vivo2, was induction of cell senescence, followed by decreased proliferative capacity and tumor growth inhibition. Senescent cells remained viable in vitro, but lost ability to divide and decreased metabolic activity, due to mitochondria alterations. Our findings demonstrate pro-senescence approach in antitumor therapy which is suggested to be less aggressive than the conventional strategies based on cancer cell killing, frequently followed by compensatory proliferation and subsequent tumor progression.