Targeting Breast Cancer-Derived Stem Cells by Dietary Phytochemicals: A Strategy for Cancer Prevention and Treatment
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Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Guddha, Bathinda 151401, India
2
Department of Urology, Nutrition, Pharmacology and Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
*
Authors to whom correspondence should be addressed.
Cancers 2022, 14(12), 2864; https://doi.org/10.3390/cancers14122864
Submission received: 27 May 2022
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Revised: 6 June 2022
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Accepted: 8 June 2022
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Published: 10 June 2022
(This article belongs to the Special Issue Molecular Mechanisms Underlying Cancer Prevention and Intervention with Bioactive Food Components)
Simple Summary
Luminal A subtype breast cancer is the most prevalent form of breast malignancy with frequent diagnosis in women. Breast cancer stem cells (BCSCs) are a rare population of cells present therein that cause cancer aggressiveness, relapse, drug-resistance, poor therapeutic outcome and a decrease in overall survival of these patients. The published literature indicates that dietary phytochemicals have the potential to target stemness and self-renewal properties in luminal A-derived BCSCs. The aim of this review is to highlight the anticancer potential of dietary phytochemicals against luminal A-derived BCSCs and their underlying mechanism(s). These findings necessitate in-depth preclinical and clinical studies on phytochemicals to explore their role in breast cancer prevention and treatment.
Abstract
Breast cancer is heterogeneous disease with variable prognosis and therapeutic response. Approximately, 70% of diagnosed breast cancer represents the luminal A subtype. This subpopulation has a fair prognosis with a lower rate of relapse than the other clinical subtypes. Acquisition of stemness in luminal A subtype modifies the phenotype plasticity to accomplish increased aggressiveness and therapeutic resistance. Therefore, targeting luminal A-derived breast cancer stem cells (BCSCs) could be a promising strategy for its prevention and treatment. Extensive studies reveal that dietary phytochemicals have the potential to target BCSCs by modulating the molecular and signal transduction pathways. Dietary phytochemicals alone or in combination with standard therapeutic modalities exert higher efficacy in targeting BCSCs through changes in stemness, self-renewal properties and hypoxia-related factors. These combinations offer achieving higher radio- and chemo- sensitization through alteration in the key signaling pathways such as AMPK, STAT3, NF-ĸB, Hedgehog, PI3K/Akt/mTOR, Notch, GSK3β, and Wnt related to cancer stemness and drug resistance. In this review, we highlight the concept of targeting luminal A-derived BCSCs with dietary phytochemicals by summarizing the pathways and underlying mechanism(s) involved during therapeutic resistance.
