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Therapeutic potential of quercetin on human breast cancer in different dimensions

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Abstract

Background

There has been an extensive range of incidence and mortality of breast cancer (BC), and the comprehensively available treatments for BC have not been completely successful in achieving satisfactory outcomes up to date.

Hypothesis

Recently, we are watching intense attention paid to the utilization of natural compounds as a novel therapeutic strategy for cancer treatment. Quercetin, a dietary flavonol in a large group of commonly consumed foods, is widely illustrated to apply inhibitory effects on cancer progression through several mechanisms including apoptosis enhancement, cell cycle arrest, metastasis and angiogenesis inhibition, antioxidant replication and estrogen receptor modulation.

Methods

We reviewed the most relevant papers published from 2009 to 2018 (except 15 articles), using “pub med” and “web of science” and the search terms “Quercetin”; “Breast cancer”; “Flavonoid”; “Apoptosis”; “Cell cycle”; “chemotherapy”; “Drug resistance”; “Metastasis; “Oxidative stress”, “Breast cancer receptors” and “Quercetin derivatives”. We selected studies on the association of quercetin with breast cancer in different dimensions.

Results

Despite the remarkable number of studies on quercetin’s efficacy, multiple aspects of this herbal compound have not been clarified well and this review provides a summarized update of the recent evidence on biologically available efficacies of quercetin which would establish a further biological basis for the potential therapeutic acquisition of quercetin as an anticancer drug.

Conclusion

Basic, epidemiological and genetic studies point to the potential role of quercetin in the treatment of breast cancer, but randomized and controlled trials are of great importance to establish the clinical efficacy of quercetin in ill or at-risk subjects.

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Abbreviations

ABC:

ATP-binding cassette transporters

AKT:

AK strain transforming also known as protein kinase B (PKB): a serine/threonine-specific protein kinase

AP-1:

Activator protein 1: a transcription factor regulating gene expression

Apaf-1:

Apoptotic protease activating factor 1: a cytoplasmic protein that forms one of the central hubs in the apoptosis regulatory network

Apo3:

Ligand of death receptor

BCL-2:

B-cell lymphoma 2: a founding member of the Bcl-2 family, regulating apoptosis

c-FLIP:

Caspase FLICE-like inhibitory protein: preventing DISC formation by binding to FADD and/or caspase-8 or -10 and TRAIL receptor 5 (DR5)

DR:

Death receptor: transmembrane proteins controlling the extrinsic pathway

FADD:

Fas-associated protein with death domain: an adaptor protein bridging member of TNFR superfamily

GADD45:

Growth arrest and DNA damage: stress sensors modulating the response of mammalian cells to stress and tumor formation

GSH:

Glutathione peroxidase: a tripeptide that act as an antioxidant and preventing cells of damage by reactive oxygen species

Hif-1α:

Hypoxia-inducible factor 1: subunit of hif transcription factor that is regulator of cellular and developmental response to hypoxia

m-TOR:

The mammalian target of rapamycin, also known as FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1): a kinase that regulates different cellular process

MAPK:

A mitogen-activated protein kinase: a type of protein kinase that activates transcription factors such as AP-1 in cells

NFAT:

Nuclear factor of activated T-cells: a family of transcription factors shown to be important in immune response. One or more members of the NFAT family are expressed in most cells of the immune system

Nrf-2:

The nuclear factor erythroid 2-related factor 2 (Nrf2): an emerging regulator of cellular resistance to oxidants which controls the expression of antioxidant response

PI3K:

Phosphatidyl inositol 3-kinase: a family of intracellular signal inducer enzymes involved in cellular functions such as cell growth, proliferation, differentiation and survival

Pin-1:

Peptidyl-prolyl cis–trans Isomerase NIMA-interacting 1: an enzyme that deregulation of this enzyme plays a role in different diseases

PKM2:

Pyruvate kinase isozyme M2 (PKM2) is metabolic-related enzymes expressed in different tissues

ROS:

Reactive oxygen spices: formed as a natural byproduct of the normal metabolism of oxygen that includes peroxides, superoxide and hydroxyl radical

SOD:

Superoxide dismutase: an important enzyme that helps in protecting against the damage of ROS

TNF:

Tumor necrosis factor: a cell signaling protein involved in systemic inflammation and acute phase reactions

TRAIL:

TNF-related apoptosis-inducing ligand: a protein functioning as a ligand that induces apoptosis

VEGF:

Vascular endothelial growth factor: a signal protein that stimulates the formation of blood vessels

MCF-7 cell line:

Michigan cancer foundation-7: estrogen, progesterone receptors positive, HER2 negative and perfect model for hormone therapy

MDA-MB-231 cell line:

M.D. Anderson-Metastasis Breast cancer-231: triple negative cell line (ER, PR and HER2 Negative) and shows intermediate response to chemotherapy

MDA-MB-468 cell line:

M.D. Anderson-Metastasis Breast cancer-468: triple-negative cell line (ER, PR and HER2 negative) and often chemotherapy responsive

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Neda Kasiri, Mahshid Rahmati, Leila Ahmadi considered equally to this work.

Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Box 8174673461, Isfahan, Iran

    Neda Kasiri, Mahshid Rahmati, Leila Ahmadi & Nahid Eskandari

  2. Applied Physiology Research Center, Isfahan Cardiovascular Research Institute, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Nahid Eskandari

  3. Autoimmune Disease Research Center, Kashan University of Medical Science, Kashan, Iran

    Hossein Motedayyen

Authors
  1. Neda Kasiri
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  2. Mahshid Rahmati
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  3. Leila Ahmadi
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  4. Nahid Eskandari
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  5. Hossein Motedayyen
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Correspondence to Nahid Eskandari.

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Kasiri, N., Rahmati, M., Ahmadi, L. et al. Therapeutic potential of quercetin on human breast cancer in different dimensions. Inflammopharmacol 28, 39–62 (2020). https://doi.org/10.1007/s10787-019-00660-y

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