Gelidiella Acerosacompounds Target NFKB Cascade in Lung Adenocarcinoma

Abstract

\n In carcinogenesis, increased metabolism, abnormal functioning of mitochondria, peroxisomes, aberrant cell signaling and prolonged inflammation can result in the overproduction of reactive oxygen species (ROS). In turn, excess ROS can upregulate the expression of various signaling pathways including the MAP kinase, PI3K/Akt and NFKB cascades in cancer. The constitutive expression of NFKB causes drug resistance in lung cancer. Hence, drugs that can enhance the antioxidant activity of enzymes and regulate the NFKB activity are of prime target to manage the drug resistance and inflammation in cancer. This study evaluated the effect of compounds present in ethyl acetate extract of Gelidiella acerosa on inflammation and on antioxidant enzymes in lung cancer. The anti-inflammatory activity was determined under in silicoandin vitro conditions. The in silico analysis showed that the phyto-constituents of G.acerosainhibit the IKBα-NFKB-p65-p50 complex in a similar way as that of doxorubicin and dexamethasone.Similarly,G.acerosatreatment enhanced the efficiency of antioxidant enzymes peroxidases and superoxide dismutase in A549 lung cancer cells. Further, the results of in vitro analysis showed that G.acerosa can inhibit the activation of NFKB, production of proinflammatory cytokines and upregulate the expression of IL 10. As inflammation causes cancer progression, the inhibition of inflammation inhibits tumorigenesis. Hence, based on the results of the study, it can be concluded that G.acerosa exerts anti- inflammatory activity through inhibition of NFKB cascade and moreover,the phyto-constituents ofG.acerosa may have the potential to treat cancer successfully.