Molecular mechanisms of flavonoids and their modulatory effects against breast cancer: A scoping review

Abstract

Background: Breast cancer is the most prevalent malignancy among women. It is a disease whose incidence and mortality rates are on the upsurge globally. Debilitating effects, cost and resistance to available chemotherapeutic interventions render them unideal. Dietary phytochemicals have been shown to have preventive and therapeutic effects. Research continues to affirm the role of flavonoids as potential chemotherapeutic agents in combating the disease. Understanding modulation of key cellular signalling pathways by flavonoids presents promising molecular targets that may be leveraged to develop better chemotherapeutic agents for breast cancer. Methods: To describe the in vitro and in vivo modulatory effects of flavonoids on molecular anti-cancer mechanisms we searched three databases. We included original articles describing modulation of cell signalling processes such as; cell cycle, apoptosis, autophagy, angiogenesis, invasion and migration which are involved in tumorigenesis. The search guidelines such as; year of publication, search strategy, study design and language informed article selection. Results: Thirty-six articles were reviewed. Modulatory effects of six subclasses of flavonoids on breast cancer tumorigenic pathways were reported. The effects included enhanced apoptosis, attenuation of; angiogenesis, cell cycle, invasion, migration and metastasis. For instance, pectolinarigenin inhibited signal transducer and activator of transcription 3 (stat3) signalling pathway in triple negative breast cancer. Whereas, sideritoflavone caused cell cycle arrest and inhibited migration in trastuzumab resistant breast cancer cells. Additionally, quercetin and ampelopsin inhibited stemness features in triple negative breast cancer cells. Conclusion: Evidently flavonoids showed significant modulatory effects on cellular signalling pathways crucial for breast cancer progression. The ability of flavonoids to act on a wide range of mechanisms as well as on aggressive breast cancer types presents an array of hope. We recommend that further studies be done to ascertain the applicability of these compounds in treatment of breast cancers.