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The combinatory effects of natural products and chemotherapy drugs and their mechanisms in breast cancer treatment

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Abstract

Breast cancer is the leading cause of cancer-related death among females. The global morbidity and mortality associated with breast cancer have recently been increasing. Surgery, radiation therapy, chemotherapy, endocrine therapy and biotargeted therapy, alone or in combination, are commonly used for breast cancer treatment. However, diverse side effects can be caused by the current treatments. Natural products derived from plants have almost no toxicity and side effects, with many functions and therapeutic activities. Many preclinical studies have reported the potential of natural products to enhance the effects of chemotherapy drugs in breast cancer treatment. The combined effects of these treatments in breast cancer are summarized in this review, as well as the in vivo and in vitro mechanisms. Natural products enhanced anti-cancer effects and apoptosis via the EGFR, PI3K-Akt, Wnt and other pathways. The toxicity, side effects, and drug resistance were reduced with the combination therapies. The combination of chemotherapy drugs and natural products could be a promising and effective strategy to treat breast cancer.

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Abbreviations

ABC transporters:

ATP-binding cassette transporters

Akt:

Protein kinase B

AMPK:

Adenosine 5′-monophosphate-activated protein kinase

APBI:

Accelerated partial-breast irradiation

Bax:

Bcl-2-like protein 4

Bcl-2:

B-cell lymphoma 2

BCRP:

Breast cancer resistance protein

BCSCs:

Breast cancer stem cells

CDK2:

Cyclin-dependent kinase 2

CDK4:

Cyclin-dependent kinase 4

CI:

Combination index

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

ERK1/2:

Extracellular regulated protein kinase 1/2

ERα:

Estrogen receptor alpha

ERβ2:

Estrogen receptor beta 2

FAK:

Focal adhesion kinase

Fas:

Fas receptor

GST:

Glutathione-S-transferase

HER-2:

Human epidermal growth factor receptor-2

HER-2+:

Human epidermal growth factor receptor-2-positive

HIF-1:

Alpha hypoxia-inducible factor-1

iPLA2 :

Independent phospholipase A2

IκBα:

Inhibitor of NF-κB alpha

MMP-9:

Matrix metalloproteinase-9

MRP1:

Multidrug resistance-associated protein 1

mTOR:

Mammalian target of rapamycin

NCCN:

National comprehensive cancer network

NF-κB:

Nuclear factor-κB

PARP-1:

Poly ADP-ribose polymerase

P-gp:

P-glycoprotein

PI3k:

Phosphoinositide 3 kinase

PR:

Progesterone receptor

Rb:

Retinoblastoma

ROS:

Reactive oxygen species

STAT3:

Signal transducer and activator of transcription 3

TNBC:

Triple-negative breast cancer

Twist1:

Twist-related protein 1

WBI:

Whole-breast irradiation

Wnt:

Wingless/integrated

p-ERK1/2:

Phosphorylated extracellular signal-regulated kinase 1/2

p-AKT:

Phosphorylated protein kinase B

AIF:

Apoptosis-inducing factor

ABCG2:

ATP-binding cassette super-family G member 2

EZH2:

Enhancer of zeste homolog 2

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Acknowledgements

This study was funded by the Asia–Pacific Cancer Research Foundation and the National Key Research and Development Program of China (2017YFC0113305).

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  1. Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, No. 19, XinJieKouWai St., Haidian District, Beijing, 100875, China

    Yubo Zhang, Huajun Li, Jing Zhang, Chaoran Zhao, Shuai Lu, Jinping Qiao & Mei Han

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  1. Yubo Zhang
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  2. Huajun Li
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  3. Jing Zhang
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  4. Chaoran Zhao
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  5. Shuai Lu
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  6. Jinping Qiao
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  7. Mei Han
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Correspondence to Jinping Qiao or Mei Han.

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Zhang, Y., Li, H., Zhang, J. et al. The combinatory effects of natural products and chemotherapy drugs and their mechanisms in breast cancer treatment. Phytochem Rev 19, 1179–1197 (2020). https://doi.org/10.1007/s11101-019-09628-w

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  • DOI: https://doi.org/10.1007/s11101-019-09628-w

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