Vanillin analogues o-vanillin and 2,4,6-trihydroxybenzaldehyde inhibit NF\u3baB activation and suppress growth of A375 human melanoma

BACKGROUND/AIM: Constitutive activation of nuclear factor kappa-B (NF\u138B) is a hallmark of various cancer types, including melanoma. Chemotherapy may further increase tumour NF\u138B activity, a phenomenon that, in turn, exacerbates drug resistance. This study aimed at preliminary screening of a panel of aromatic aldehydes, including vanillin, for cytotoxicity and suppression of tumour cell NF\u138B activity. MATERIALS AND METHODS: The cytotoxic and NF\u138B-inhibitory effects of 10 aromatic aldehydes, including vanillin, were investigated in cultured A375 human melanoma cells. Each compound was assayed alone and in combination with the model NF\u138B-activating drug doxorubicin. The most promising analogues were then tested alone and in combination with 4-hydroperoxycyclophosphamide in vitro, and with cyclophosphamide in mice bearing A375 xenografts. RESULTS: The vanillin analogues o-vanillin and 2,4,6-trihydroxybenzaldehyde exhibited cytotoxicity against cultured A375 cells, and inhibited doxorubicin- and 4-hydroperoxycyclophosphamide-induced NF\u138B activation. They also suppressed A375 cell growth in mice. CONCLUSION: o-vanillin and 2,4,6-trihydroxybenzaldehyde deserve further evaluation as potential anticancer drugs