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

Marton, Annamária and Kusz, Erzsébet and Kolozsi, Csongor and Tubak, Vilmos and Zagotto, G. and Buzás, Krisztina and Vizler, Csaba (2016) Vanillin Analogues o-Vanillin and 2,4,6-Trihydroxybenzaldehyde Inhibit NF kappa B Activation and Suppress Growth of A375 Human Melanoma. Anticancer Research, 36 (11). pp. 5743-5750. ISSN 0250-7005 (print), 1791-7530 (online)

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Abstract

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.

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