Inhibition of thioredoxin reductase 1 by evernic and vulpinic acids: a promising anticancer strategy on A549 cells

TrxR1 (Thioredoxin reductase 1) is overexpressed in several types of cancer, containing lung cancer, which is closely linked to metastasis. Hence, TrxR1 has emerged as a target for cancer therapies. In this study, it was aimed to survey whether lecanoric (LA), evernic acid (EA), and vulpinic acid (VA) exert an anticancer effect on lung cancer (A549) cells by targeting the TrxR1 protein. The findings indicated that VA elicited a more notable cytotoxic activity in A549 cells (36.21 µg/mL) at a lower IC₅₀ value than EA (139.09 µg/mL). Whereas, LA exhibited very low cytotoxic effect in A549 cells. The flow cytometry and qPCR analyses revealed that VA was superior to EA in inducing apoptosis and necrosis in A549 cells. Moreover, the wound healing assay revealed that both EA and VA considerably inhibited the migration of A549 cells. Furthermore, EA and VA markedly decreased protein expression and enzyme activity of TrxR1 in A549 cells. All these findings revealed that EA and VA possess anticancer activities by targeting TrxR1 in A549 cells. Hence, EA and VA can be proposed as candidates for use as a potential chemotherapeutic agent for lung cancer.