The ethanol extract of Eleutherine americana Merr. inhibited NF-κB and cyclin D1 expression in melanoma cell line A375.S2

Abstract

Melanoma is a type of cancer derived from melanocytes, and the incidence and mortality are predicted to increase. Melanoma therapy faces various challenges, especially primary and secondary resistance, highlighting the need for alternative chemotherapy that is suitable for each case characteristic. Eleutherine americana Merr. has been found to have a potential cytotoxic effect on melanoma cells. However, its target of action was not yet known. This study aimed to address this knowledge gap by exploring the ethanol extract of Eleutherine americana Mer (EEEA)'s ability to inhibit NF-κB and cyclin D1 expression and attempted to predict its target of action. Three different concentrations of EEEA were tested on the A375.S2 melanoma cell line. NF-κB and cyclin D1 expression was observed semiquantitatively through immune histochemical staining with primary antibody anti-NF-κB/p65 or anti-cyclin D1. The RNA helicase DDX5/p68 which was predicted to be the target of EEEA was tested in silico. EEEA significantly decreased NF-κB/p65 and cyclin D1 expression at concentrations of 25 and 50µg/ml. Twelve EEEA secondary metabolites were predicted to have strong energy-binding with ATP/ADP-binding pocket and RNA-binding pocket of DDX5/p68. The EEEA’s secondary metabolites with the strongest binding energy in ATP/ADP-binding pocket DDX5/p68 were eleuthoside B, eleutherinoside A, and eleutherinoside D, while in RNA-binding pocket were eleutherinoside-E, eleutherinoside-D, eleutherinoside-B, and eleutherinoside-C. Therefore, EEEA potentially inhibits the progression of melanoma, especially if overexpressing cyclin D1, NF-κB, and DDX5/p68.