Anticancer efficacy of Spiruchostatin A: current insights into histone deacetylase inhibition and oncologic applications.

Abstract

Spiruchostatin A also referred to as YM753 and OBP801, a cyclic peptide-based natural product derived from Pseudomonas sp., is distinguished by its potent inhibition of Class I histone deacetylases (HDACs). The modulation of epigenetic mechanisms by HDAC inhibitors is fundamental for altering gene expression related to cell growth, apoptosis, and differentiation, highlighting their potential in oncologic therapies. This updated review assesses the antitumor efficacy of Spiruchostatin A across diverse cellular and animal models, scrutinizing its viability as a therapeutic agent against various cancers. A systematic literature review was executed by searching databases such as PubMed/MedLine, Scopus, and Web of Science from October 2022 to February 2023. The inclusion criteria focused on studies involving Spiruchostatin A in the context of cancer treatment, including in vitro and in vivo models. The review concentrated on the compound's mechanistic action, biological activity, and clinical applicability. Spiruchostatin A has demonstrated significant antitumor activities, including inducing apoptosis and inhibiting tumor growth effectively in multiple models. Its therapeutic potential is particularly noted in synergistic applications with other anticancer agents, enhancing its efficacy. Mechanistically, the compound facilitates chromatin relaxation and transcriptional activation of key tumor suppressor genes through increased histone acetylation. Spiruchostatin A exhibits substantial potential as an anticancer agent through effective HDAC inhibition and subsequent epigenetic modifications of cancer cell biology. However, comprehensive clinical trials are imperative to validate its efficacy and safety profiles comprehensively. Future research is warranted to elucidate detailed molecular mechanisms and to develop biomarkers for predicting treatment response. Comprehensive longitudinal clinical studies are also critical to establish Spiruchostatin A's role within the broader oncological therapeutic regimen, along with the exploration of its analogs for improved therapeutic outcomes.