The Anticancer Effect of Napabucasin (BBI608), a Natural Naphthoquinone

Napabucasin, also known as BBI608, is a natural naphthoquinone that was initially identified as an inhibitor of cancer cell stemness. Evidence from both in vitro and in vivo studies has shown that napabucasin exhibits significant anticancer effects across various cancer types. It inhibits cancer cell proliferation, induces apoptosis and cell cycle arrest, and suppresses metastasis and recurrence. The primary mechanism behind these anticancer activities involves the inhibition of cancer stemness through the targeting of signal transducer and activator of transcription 3 (STAT3) and the downregulation of its associated genes. Additionally, several novel molecular targets for napabucasin have been identified, including NAD(P)H oxidoreductase 1 (NQO1) and thioredoxin reductase 1 (TrxR1). Overall, napabucasin holds promise as a potential anticancer agent for multiple malignancies. This mini-review will briefly highlight its anticancer potential and underlying molecular mechanisms.