An updated overview of anticancer effects of alternariol and its derivatives: underlying molecular mechanisms

Abstract

Alternariol is a toxic metabolite of Alternaria fungi and studies have shown multiple potential pharmacological effects. To outline the anticancer effects and mechanisms of alternariol and its derivatives based on database reports, an updated search of PubMed/MedLine, ScienceDirect, Web of Science, and Scopus databases was performed with relevant keywords for published articles. The studies found to suggest that this mycotoxin and/or its derivatives have potential anticancer effects in many pharmacological preclinical test systems. Scientific reports indicate that alternariol and/or its derivatives exhibit anticancer through several pathways, including cytotoxic, reactive oxygen species leading to oxidative stress and mitochondrial dysfunction-linked cytotoxic effect, anti-inflammatory, cell cycle arrest, apoptotic cell death, genotoxic and mutagenic, anti-proliferative, autophagy, and estrogenic and clastogenic mechanisms. In light of these results, alternariol may be one of the hopeful chemotherapeutic agents.

Keywords: alternariol; apoptosis; cancer; chemotherapy; cytotoxic effect; molecular targets; mycotoxin.

FIGURE 1

The chemical structures of Alternariol and its derivatives and their anticancer potential mechanisms. Symbols: ↑ (increased), ↓(decreased).

FIGURE 2

Possible mechanisms of anti-cancer activity of alternariol: (A) Alternariol induces apoptosis through targeting multiple deregulated signaling pathways in cancer cells, (B) Possible autophagy mechanism of alternariol through the activation of Sestrin2-AMPK-mTOR-S6K signaling pathway, (C) alternariol moderates the activity of cyclins and cyclin-dependent kinases to induce cell cycle arrest at G2/M phase. Abbreviations and symbols: ↑ increased, ↓ decreased, CDK cyclin-dependent kinase, COX-2 cyclooxygenase-2, CREB cAMP response element-binding, IFN interferon, IL interleukin, iNOS inducible nitric oxide synthase, LPS lipopolysaccharide, MAPK mitogen-activated protein kinase, mTOR mammalian target of rapamycin, PGE2 prostaglandin E2, PKA protein kinase A, ROS reactive oxygen species.