Marine Animal-Derived Compounds and Autophagy Modulation in Breast Cancer Cells

Claudio Luparello

doi:10.3390/foundations1010002

Abstract

It is known that in breast cancer biology, autophagy mainly plays a cytoprotective and anti-apoptotic role in vitro, being conceivably responsible for cell resistance to drug exposure and a higher metastatic attitude in vivo. Thus, the development of novel autophagy-targeting agents represents a valuable strategy to improve the efficacy of anticancer interventions. It is widely acknowledged that the enormous biodiversity of marine organisms represents a highly promising reserve for the isolation of bioactive primary and secondary metabolites targeting one or several specific molecular pathways and displaying active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of marine animal-derived extracts or isolated compounds which exert a modulatory effect on the autophagic process in breast cancer cells and list them with respect to the taxonomical hierarchy of the producing species. Where available, the molecular and biochemical aspects associated with the molecules or extracts under discussion will be also summarized.

Highlights

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It is widely acknowledged that the enormous biodiversity of marine organisms represents a highly promising reserve for the isolation of bioactive primary and secondary metabolites targeting one or several specific molecular pathways and displaying active pharmacological properties against a variety of diseases
The role played by autophagy in cancer biology is complex since it exhibits a dual nature, being involved both in oncogenesis and in oncosuppression in different conditions, which take a variety of cell types, cycle phase distributions, genetic makeups, and microenvironmental scenarios into account

Summary

A Brief Insight into Autophagy and Breast Cancer Cells

The term “macroautophagy”, hereafter referred as “autophagy”, relates to a ubiquitous cellular function that encompasses the engulfing of selected cytoplasmic components by double-membrane structures called autophagosomes, as well as their subsequent delivery to lysosomes and degradation by resident hydrolases Such a process guarantees the removal and turnover of damaged and aged cytoplasmic organelles or protein aggregates and the recycling of breakdown products for reutilization and energy production, which bring the autophagic flux to completion. ATGs are traditionally classified in functional groups according to whether they operate in the initiation of autophagosome formation, the elongation of phagophores, maturation of autophagosomes, or fusion with late endosomes or lysosomes Their expression undergoes upstream control by an intricate signalization network which involves AKT/mechanistic targeting of rapamycin (mTOR)-dependent and independent (e.g., mucolipin Ca++ channel-mediated) pathways, whose understanding is still incomplete [3,4]. With the warning to take the specific breast cancer subtype and treatment used into consideration, the cumulative preclinical data obtained prompt the development of novel autophagy-targeting agents as a valuable strategy to improve the efficacy of anticancer interventions

The Marine Animal Species as a Source of Bioactive Molecules

Autophagy Modulators from Mollusca

Conclusions