Polyphenols as Promising Drugs against Main Breast Cancer Signatures

Abstract

Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs) and epidermal growth factor receptor 2 (HER2). Tumors with none of these receptors are classified as triple negative breast cancer (TNBC) and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation.

Conjugated Physiological Resveratrol Metabolites Induce Senescence in Breast Cancer Cells: Role of p53/p21 and p16/Rb Pathways, and ABC Transporters

“…Resveratrol (RSV), a natural stilbene found in several plant foods (such as grapes, berries, and peanuts), is one of the most relevant molecules to exert anticarcinogenic effects through many different mechanisms of action, including cell proliferation arrest, initiation and progression inhibition, and/or apoptosis induction against various types of cancer, including BC . Notwithstanding, despite the promising in vitro effects of many polyphenols showing suppressing actions against BC, the clinical evidence is scarce . In this regard, most in vitro studies carried out with polyphenols (and hence RSV) against BC have followed the wrong approach of traditional in vitro assays without considering the polyphenols’ bioavailability, metabolic transformations, and tissue disposition to evaluate and attribute their potential anticancer effects …”

“…[4,5] Notwithstanding, despite the promising in vitro effects of many polyphenols showing suppressing actions against BC, the clinical evidence is scarce. [4,6] In this regard, most in vitro studies carried out with polyphenols (and hence RSV) against BC have followed the wrong approach of traditional in vitro assays without considering the polyphenols' bioavailability, metabolic transformations, and tissue disposition to evaluate and attribute their potential anticancer effects. [7] Animal and human studies have demonstrated low bioavailability and rapid clearance of RSV from the circulation, which is related to its extensive phase-II metabolism catalyzed by enzymes known as transferases, mainly UDP glucuronyl transferases and sulfotransferases (EC number 2.4.1.17 and 2.8.2, respectively), as well as to its microbiota-derived metabolite dihydroresveratrol (DH-RSV).…”

Alternative Treatments for Cancer Prevention and Cure [Part 1]

“…Jazzara, et al [380] concluded that λ-carrageenan ( Figure 6f) (sulfated galactans found in certain red seaweeds) could be a promising bioactive polymer, showed a remarkable inhibitory effect on MDA-MB-231(triple negative breast cancer cell line) cell migration [381]. Several studies support polyphenols [382][383][384][385][386], flavonoids [387][388][389][390][391][392][393][394][395], fucoidan [396][397][398][399][400][401][402][403][404][405][406][407], lutein/zeaxanthin [408][409][410][411][412], other seaweed alkaloids, peptides, tannins and polysaccharides [413][414][415][416][417][418][419][420][421][422][423][424][425] in breast cancer management ( Figure 7).…”

Seaweeds: An Extensive Review of Medicinal Values

“…Jazzara et al [170] concluded that λ-carrageenan (sulfated galactans found in certain red seaweeds) could be a promising bioactive polymer, showed a remarkable inhibitory effect on MDA-MB-231(triple negative breast cancer cell line) cell migration [171]. Several studies support polyphenols [172][173][174][175][176], flavonoids [177][178][179][180][181][182][183][184][185][186], fucoidan [159,160,166,[187][188][189][190][191][192][193][194][195], lutein/zeaxanthin [196][197][198][199][200], other seaweed alkaloids, peptides, tannins and polysaccharides [132,164,[201][202][203][204][205][206][207][208][209][210] in breast cancer management. The number of deaths from colorectal cancer in Japan continues to increase [211], it is the third most common diagnosis and second deadliest malignancy for both sexes combined…”