Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential

Abstract

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.

Bioactive Glasses Modulate Anticancer Activity and Other Polyphenol-Related Properties of Polyphenol-Loaded PCL/Bioactive Glass Composites

“…Although the majority of the beneficial effects of polyphenols are attributed to their antioxidant activity, there is evidence that polyphenols may also possess prooxidant properties . ROS-mediated cancer cell cycle arrest and cell death by apoptosis induced by DNA damage, among others, have been identified as the main molecular pathways responsible for the anticancer activity of polyphenols, also in OS. , …”

Mechanistic insights into targeting caspase‐3 activation and alveolar macrophage pyroptosis by Ephedra and bitter almond compounds for treating pediatric pneumonia via network pharmacology and bioinformatics

“…Caspase‐3 can specifically cleave the key molecule GSDMD of pyroptosis, releasing the N‐terminal domain to form N‐GSDMD, which promotes cell membrane perforation and pyroptosis (Jiang et al., 2020). In addition, the generation of N‐GSDME can increase cell membrane permeability, promote the release of cytochrome C, and induce cell apoptosis mediated by caspase‐3 (Alaswad et al., 2021; Wei et al., 2022). Downregulation of caspase‐3 can alleviate the apoptosis of alveolar epithelial cells induced by Mycoplasma pneumonia and reduce the necrosis and apoptosis of alveolar macrophages (Shi et al., 2017).…”

Natural Polyphenols as Modulators of Etoposide Anti-Cancer Activity

“…Polyphenols exert their potential in anti-cancer therapy via promoting apoptosis and cell senescence, regulating autophagy, and inhibiting proliferation and migration of cancer cells. They can induce cellular stress and catabolism: through an increase in reactive oxygen species (ROS) and a decrease in cellular antioxidants such as glutathione (GSH), interaction with chemotherapy agents and the reduction or reversal of multidrug resistance [ 7 ]. Polyphenols can change epigenetic modifications, such as DNA methylation and histone modifications, as well as regulate non-coding miRNAs expression, which modulates gene expression.…”

“…In addition, some studies indicate that polyphenols are less cytotoxic to normal cells compared to cancer cells. As components of complementary or supportive therapy, they could have a protective and health-promoting effect on the patient’s body [ 2 , 4 , 7 , 8 ].…”