Vanillin Analogues o-Vanillin and 2,4,6-Trihydroxybenzaldehyde Inhibit NF kappa B Activation and Suppress Growth of A375 Human Melanoma

Background/Aim: Constitutive activation of nuclear factor kappa-B (NF kappa B) is a hallmark of various cancer types, including melanoma. Chemotherapy may further increase tumour NF kappa B 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 kappa B activity. Materials and Methods: The cytotoxic and NF kappa B-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 kappa B-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 kappa B activation. They also suppressed A375 cell growth in mice. Conclusion: o-vanillin and 2,4,6-trihydroxybenzaldehyde deserve further evaluation as potential anticancer drugs