Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer

Abstract

Cancer is one of the most serious diseases endangering human health. In view of the side effects caused by chemotherapy and radiotherapy, it is necessary to develop low-toxic anti-cancer compounds. Polyphenols are natural compounds with anti-cancer properties and their application is a considerable choice. Pro-senescence therapy is a recently proposed anti-cancer strategy and has been shown to effectively inhibit cancer. It is of great significance to clarify the mechanisms of polyphenols on tumor suppression by inducing senescence. In this review, we delineated the characteristics of senescent cells, and summarized the mechanisms of polyphenols targeting tumor microenvironment and inducing cancer cell senescence for cancer prevention and therapy. Although many studies have shown that polyphenols effectively inhibit cancer by targeting senescence, it warrants further investigation in preclinical and clinical studies.

Cytotoxic Effect of Vanicosides A and B from Reynoutria sachalinensis against Melanotic and Amelanotic Melanoma Cell Lines and in silico Evaluation for Inhibition of BRAFV600E and MEK1

“…It should be mentioned that in some cases, such as oxygen-radical injury of cells, two cell death mechanisms—apoptosis and permeability transition pore (PTP)-mediated necrosis—occur simultaneously [ 29 ]. Vanicosides, like other polyphenols, could promote oxidative stress in cancer cells and lead to cell death simultaneously through various mechanisms [ 7 ]. Research showing the effect of vanicosides on mitochondrial membrane permeability, in particular, on mitochondrial outer membrane permeabilization (MOMP: plays an essential role in apoptosis) and permeability transition pore (PTP; associated with necrosis), is recommended in the future [ 29 ].…”

“…The results from the annexin assay are also very similar for lower concentrations of vanicosides. Different doses could reflect different mechanisms of cell death, which is observed in studies with polyphenols, where high doses of drugs promote apoptosis, but low concentrations of drugs exert a pro-senescence effect [ 7 ].…”

“…Among natural products of plant origin, polyphenols have been found to target different hallmarks of cancer cells, often interfering with several of them at once, such as promoting apoptosis, regulating autophagy and inhibiting proliferation, and as well, they modulate the metabolic properties of cancer cells and the affect tumor-induced immunosuppressive behavior through the modulation of T-regulatory (Treg) cell populations and many others, including epigenetic modulation [ 7 , 8 ]. The natural plant compounds have also proved to be effective in repressing cancer chemoresistance [ 8 ].…”

Bioactive (Poly)phenols, Volatile Compounds from Vegetables, Medicinal and Aromatic Plants

“…As mentioned previously, polyphenols are natural compounds present in many vegetables and MAPs. In the human body, the majority of polyphenols have poor absorptions and they are retained in the intestine for more time where they can promote beneficial effects, specifically by affecting the gut microbiota [ 96 , 97 , 98 ]. This leads to a mutual reaction between polyphenolic compounds and gut microbiota.…”

“…This leads to a mutual reaction between polyphenolic compounds and gut microbiota. The polyphenols are biotransformed into low-molecular-weight phenolic metabolites by gut microbiota resulting in an increase in polyphenol’s bioavailability, responsible for the health effects derived from the consumption of polyphenol-rich plants, which may differ from the native compound found in the plants [ 97 , 98 , 99 , 100 , 101 , 102 ]. The properties of polyphenols are dependent on the bioactive metabolites produced when they are metabolised by the microbiota [ 103 ].…”