Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential

• Published in: International journal of molecular sciences 2021-03, Vol.22 (6), p.3085
• Main Authors: Alaswad, Hamza A, Mahbub, Amani A, Le Maitre, Christine L, Jordan-Mahy, Nicola
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis; Autophagy - drug effects; Bioavailability; Caspase; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell death; Cell proliferation; Chemotherapy; Cytochrome c; DNA damage; glutathione; Humans; Inflammation; Kinases; leukaemia; Leukemia; Leukemia - drug therapy; Leukemia - pathology; Membrane potential; Mitochondria; Models, Biological; Multidrug resistance; NF-κB protein; Oxidants; Oxidizing agents; Phagocytosis; Plants; Polyphenols; Polyphenols - chemistry; Polyphenols - pharmacology; Polyphenols - therapeutic use; reactive oxygen species; Reactive Oxygen Species - metabolism; Review; Stat3 protein; Toxicity; Transcription factors; Tumor necrosis factor-TNF; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22063085

Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Plant-derived polyphenols have been identified as potent anti-cancer agents and have been shown to work synergistically with standard chemotherapy agents in leukaemia cell lines. Polyphenols have multiple mechanisms of action and have been reported to decrease cell proliferation, arrest cell cycle and induce apoptosis via the activation of caspase (3, 8 and 9); the loss of mitochondrial membrane potential and the release of cytochrome c. Polyphenols have been shown to suppress activation of transcription factors, including NF-kB and STAT3. Furthermore, polyphenols have pro-oxidant properties, with increasing evidence that polyphenols inhibit the antioxidant activity of glutathione, causing oxidative DNA damage. Polyphenols also induce autophagy-driven cancer cell death and regulate multidrug resistance proteins, and thus may be able to reverse resistance to chemotherapy agents. This review examines the molecular mechanism of action of polyphenols and discusses their potential therapeutic targets. Here, we discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism are essential to evaluate their clinical use.