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Phytometabolites as modulators of breast cancer: a comprehensive review of mechanistic insights

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Medical Oncology Aims and scope Submit manuscript

Abstract

Breast cancer (BC) is a highly debilitating malignancy affecting females globally and imposing a substantial burden on healthcare systems in both developed and developing nations. Despite the application of conventional therapeutic modalities such as chemotherapy, radiation therapy, and hormonal intervention, BC frequently exhibits resistance, necessitating the urgent development of novel, cost-effective, and accessible treatment strategies. In this context, there is a growing scientific interest in exploring the pharmacological potential of chemical compounds derived from botanical sources, which often exhibit notable biological activity. Extensive in vitro and in vivo investigations have revealed the capacity of these compounds, referred to as phytochemicals, to attenuate the metastatic cascade and reduce the risk of cancer dissemination. These phytochemicals exert their effects through modulation of key molecular and metabolic processes, including regulation of the cell cycle, induction of apoptotic cell death, inhibition of angiogenesis, and suppression of metastatic progression. To shed light on the latest advancements in this field, a comprehensive review of the scientific literature has been conducted, focusing on secondary metabolite agents that have recently been investigated and have demonstrated promising anticancer properties. This review aims to delineate their underlying mechanisms of action and elucidate the associated signaling pathways, thereby contributing to a deeper understanding of their therapeutic potential in the context of BC management.

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Data Availability

There is no data to be disclosed separately for the current review article.

Abbreviations

MCF-7:

Michigan Cancer Foundation-7

T47D:

Differentiated epithelial substrain

MDA-MB-453:

MD Anderson-Metastatic Breast-453

Bcl-2:

B-cell lymphoma 2

VEGF:

Vascular endothelial growth factor

FOXM1-ER-α:

Forkhead box M1 Estrogen receptor α

EMT:

Epithelial–mesenchymal transition

PTEN:

Phosphatase and tensin homolog

CDH1:

E-cadherin

CD44:

Cluster of differentiation 4

Akt:

Ak strain transforming

SP1:

Specificity protein1

Cav-1:

Caveolin-1;

P-gp:

P-glycoprotein

hTERT:

Human Telomerase Reverse Transcriptase

NF-κB:

Nuclear factor-κB

CDK2:

Cyclin-dependent kinase 2

ZER:

Zerumbone

CXCR4:

C-X-C motif chemokine receptor 4

IC50 :

Inhibitory concentration

McTN:

Microtentacles

RUNX2:

Runt-related transcription factor 2

CDK6:

Cyclin-dependent kinase 6

ATF-3:

Activating transcription factor 3

FBI‐1:

Factor that binds to inducer of short transcripts‐1

mTOR:

Mammalian target of rapamycin

LOX:

Lysyl oxidase

MDM2:

Mouse double minute 2 homolog

BRCA1:

Breast Cancer gene 1

p21Cip1:

Cyclin-dependent kinase inhibitor p21

EphA2:

Ephrin type-A receptor 2

Twist1:

Twist-related protein 1

STAT3:

Signal transducer and activator of transcription 3

CCL2:

CC-Chemokine ligand 2

POLD1:

Polymerase δ catalytic subunit gene 1

JAK/STAT:

Janus kinase/signal transducers and activators of transcription

MAP kinase:

Mitogen-activated protein kinase

BNIP3:

Bcl-2 interacting protein 3

BIRC5:

Baculoviral IAP Repeat Containing 5

TNFα:

Tumor necrosis factor α

GADD45A:

Growth arrest and DNA damage-inducible 45 alpha

HRK:

Harakiri

TNFRSF25:

TNF receptor superfamily member 25

TNFRSF11B:

Tumor necrosis factor receptor superfamily member 11B

TP53:

Tumor protein P53

GM-CSF:

Granulocyte macrophage-colony-stimulating factor

TSLP:

Thymic stromal lymphopoietin

4EBP1:

4E-binding protein 1

Nrf2:

Nuclear factor erythroid 2-related factor 2

MSH2:

MutS homolog 2

MGMT:

O6-Methylguanine-DNA methyltransferase

XPC:

Xeroderma pigmentosum complementation gene

OGG1:

8-Oxoguanine DNA glycosylase

H3K9:

Histone H3 lysine 9

TXNRD2:

Thioredoxin reductase 2

HIF-1:

Hypoxia-inducible factor 1

GPR30 :

G Protein-Coupled Receptor

HOTAIR:

HOX transcript antisense intergenic RNA

TXNIP:

Thioredoxin-interacting protein

LC3-II:

LC3 phosphatidylethanolamine conjugate

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Acknowledgements

Authors are thankful to the Department of Science and Technology (DST), Government of India for providing Departmental DST-FIST grant (SR/FST/LSI-656/2016) to the Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, India.

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  1. Department of Pharmaceutical Sciences and Natural Products, School of Pharmaceutical Sciences, Central University of Punjab, Bathinda, Punjab, 151401, India

    Priyanka Sharma, Khushi Gupta, Sumit Kumar Khandai & Suresh Thareja

  2. Laboratory of Woody Plants and Crops Biology, University of Orleans, Orleans, France

    Sonia Malik

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  1. Priyanka Sharma
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Contributions

P.S. conceptualized and supervised the overall studies, critically reviewed, and wrote the final draft of the manuscript. K.G. performed data curing. SKK. performed data curing. SM. contributed toward review and editing. S.T. provided broad direction for the study, supervised, critically reviewed, and finally approved the manuscript.

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Correspondence to Suresh Thareja.

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Sharma, P., Gupta, K., Khandai, S.K. et al. Phytometabolites as modulators of breast cancer: a comprehensive review of mechanistic insights. Med Oncol 41, 45 (2024). https://doi.org/10.1007/s12032-023-02269-2

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