Do Marine Polysaccharides Carrageenans Modulate Non-apoptotic Regulated Cell Deaths ? (a Review)

• Published in: Current pharmacology reports 2023-12, Vol.9 (6), p.580-601
• Main Authors: Tkachenko, Anton, Onishchenko, Anatolii, Prokopiuk, Volodymyr
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Molecular Medicine; Pharmacology/Toxicology; Topical Collection on Natural Products: From Chemistry to Pharmacology
• ISSN: 2198-641X; 2198-641X
• DOI: 10.1007/s40495-023-00339-7

Purpose of Review A growing number of studies indicate that a network of regulated cell death (RCD) pathways plays a vital role in tumorigenesis suggesting its targeting to be a promising therapeutic avenue for cancer treatment. In this review, we firstly systematically summarize the current knowledge on the impact of carrageenans on different non-conventional non-apoptotic RCDs and explore a therapeutic potential of carrageenans as RCDs-modulating agents. Furthermore, we cover the knowledge gaps and controversies in our understanding of cell death-related carrageenan-mediated effects and highlight the directions of further research aiming at studying the pharmacological potential of carrageenans. Recent Findings A compelling body of evidence indicates that non-apoptotic RCDs, including necroptosis, ferroptosis, pyroptosis, and autophagy-related cell death, are involved in modulating tumorigenesis and immune response in cancer. Recent advances in our understanding of the role of distinct non-apoptotic RCDs suggest that pharmacological modulation of diverse RCDs is a tempting anti-cancer therapeutic strategy. In particular, carrageenans, which are a group of heterogenous anionic hydrocolloids of polysaccharide nature widely used as food additives (E407 and E407a), have been shown to have anti-viral, anti-cancer, and immunomodulatory activity. The anti-cancer activity of carrageenans is attributed to a certain extent to activation of apoptosis, but the effects of carrageenan on other RCD modes, which can be targeted in oncopathology, are poorly summarized. Summary Anti-cancer, immunomodulatory, and anti-viral properties of marine polysaccharides carrageenans are at least partly explained by their modulation of RCD modalities, primarily pyroptosis. Thus, carrageenans can be considered promising RCD-regulating agents, which can be therapeutically exploitable. Furthermore, we emphasize the need to consider induction of non-conventional RCDs as one of the possible molecular mechanisms of carrageenan toxicity. Graphical Abstract