Abstract
Breast cancer (BC) remains the second most common cause of cancer-related deaths in women in the US, despite advances in detection and treatment. In addition, breast cancer survivors often struggle with long-term treatment related comorbidities. Identifying novel therapies that are effective while minimizing toxicity is critical in curtailing this disease. Flavonoids, a subclass of plant polyphenols, are emerging as promising treatment options for the prevention and treatment of breast cancer. Recent evidence suggests that in addition to anti-oxidant properties, flavonoids can directly interact with proteins, making them ideal small molecules for the modulation of enzymes, transcription factors and cell surface receptors. Of particular interest is the ability of flavonoids to modulate the tumor associated macrophage function. However, clinical applications of flavonoids in cancer trials are limited. Epidemiological and smaller clinical studies have been largely hypothesis generating. Future research should aim at addressing known challenges with a broader use of preclinical models and investigating enhanced dose-delivery systems that can overcome limited bioavailability of dietary flavonoids. In this review, we discuss the structure-functional impact of flavonoids and their action on breast tumor cells and the tumor microenvironment, with an emphasis on their clinical role in the prevention and treatment of breast cancer.
Highlights
Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide and the second most common cause of cancer-related mortality in women in the US [1,2]
We have earlier reported that apigenin, through its direct interaction with heterogeneous ribonuclear protein A2 (hnRNPA2), can reduce the levels of splice isoform of cellular FLICE-like inhibitory protein (c-FLIP) (c-FLIPS ) and caspase-9 in MDA-MB-231, two key RNA isoforms that when translated play a role in inhibiting apoptosis in cancer cells [98]
In the Breast Cancer Prevention P-1 trial and World Health Initiative trial I, two among the many clinical trials conducted on obesity-BC relation, found that obesity was strongly associated with higher premenopausal [187] and postmenopausal BC risk [188], respectively
Summary
Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide and the second most common cause of cancer-related mortality in women in the US [1,2]. Flavonoids, plant polyphenols broadly present in fruits and vegetables, are emerging as promising arsenals for the prevention and treatment of cancer and other chronic inflammatory diseases [5,6,7,8,9]. Antioxidants 2019, 8, 103 of enzymes, transcription factors and receptors [10] These novel properties of flavonoids propose new platforms to modulate tumor signaling, overcome chemo-resistance and re-educate the tumor microenvironment (TME). Unraveling these novel mechanisms of action of flavonoids offers great clinical opportunities. We discuss the structure-functional impact of flavonoids and their action on tumor cells and TME, with an emphasis on their clinical role in the prevention and treatment of breast cancer
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