Mozhdeh Zamani, Farima Safari, Morvarid Siri, Somayeh Igder, Niloofar khatami, Sanaz Dastghaib, Pooneh Mokarram

Abstract

Purpose: Colorectal cancer (CRC) remains a global health challenge with limited treatment success due to drug resistance. Recent research highlights the potential of small molecules to modulate CRC by targeting epigenetics or autophagy pathways. This systematic review explores the epigenetic effect of small molecules on autophagy in CRC, aiming to identify novel therapeutic strategies.

Methods: Following PRISMA guidelines, we systematically reviewed 508 studies from PubMed, Scopus, and Web of Science databases until August 13, 2023.

Results: Eight studies met inclusion criteria, examining the role of small molecules as epigenetic modulators (Histone acetylation/deacetylation, DNA methylation/demethylation and gene expression regulation by miRNAs) influencing the autophagy pathway in CRC. The studies encompassed in vitro and animal model in vivo studies. Small molecules exhibited diverse effects on autophagy in CRC. For instance, panobinostat promoted autophagy leading to CRC cell death, while aspirin inhibited autophagy flux, reducing aspirin-mediated CRC cell death. The epigenetic modulation of autophagy by various small molecules differently affects their anticancer effect, which underscores the complexity of therapeutic interventions.

Conclusion: Understanding the intricate dynamics among small molecules, epigenetic modifications, and autophagy in CRC is crucial for developing targeted therapeutic strategies. Considering the dual role of autophagy in tumorigenesis and tumor suppression, administration of these small molecules may differently affect the cancer cell fate and drug response or resistance based on their effect on the autophagy pathway. Therefore, recognition of the epigenetics mechanism of anticancer small molecules on autophagy may contribute to deciding how to prescribe them for better CRC treatment.

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