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Role of natural P-gp inhibitor in the effective delivery for chemotherapeutic agents

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Abstract

Multi-drug resistance has shown to be one of the leading threats faced currently in many chemotherapeutic agents. Permeability glycoprotein (P-gp) is an efflux transporter in membrane, an integral part of ATP-binding cassette (ABC) transporters widely distributed in the body for cellular uptake. It is present enormously in cancerous cells and is in charge of generating transporter mediated resistance to treatments of tumorous cells in addition to blocking the entry of chemotherapeutic drugs into the cell. Natural P-gp inhibitors are derived from natural plant sources possessing basic structures like alkaloids, flavonoids, phenolics, terpenoids, saponins, sapogenins, sterols, coumarins and miscellaneous structures acting on P-gp substrate for inhibition of multi-drug resistance via inhibiting the efflux pump. They do not depict their action on the healthy cells and thus it is proven to be more effective and less toxic than synthetic P-gp inhibitor leading to enhancement in bioavailability of chemotherapeutic drugs. The significant objective of the present review is surfing through the impact of natural P-gp inhibitors having basic structures derived from the plant sources and how it inhibits the resistance of chemotherapeutic drugs together with how well it delivers chemotherapy medicines.

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Data availability

Data will be made available on request.

Abbreviations

P-gp:

Permeability glycoprotein

ABC:

ATP-Binding Cassette

MDR:

Multi-drug resistance

DNA:

Deoxyribonucleic acid

MRP:

Multi-drug associated Proteins

BCRP:

Breast Cancer resistance protein

BBB:

Blood–Brain barrier

VCR:

Vincristine

HCT-8:

Cells isolated from large intestine of an adenocarcinoma patient.

HIF-1-alpha:

Hypoxia-inducible factor-1-alpha

PI3K:

Phosphatidylinositol 3-kinase

AKT:

Protein kinase B

ERK:

Extracellular signal-regulated kinase

A549T:

Cells isolated from the lung cancer patient

TGF-1-β:

Transferring growth factor β

OPB:

8-Oxo-epiberberine

SMAD3:

Protein-coding gene

SK-OV-3:

Cells isolated from ovary having ovarian carcinoma

SK-MEL-2:

Cells isolated from malignant melanoma patient

XF 498:

Human CNS solid tumour

MDA-MB cell:

Human breast cancer cell line

CaCO2 cell:

Cell line of human colorectal adenocarcinoma cells

MCF-7:

Epithelial cell line of breast cancer

MDA-MB-231:

Epithelial cell line of breast cancer obtained via pleural effusion

Hep G2:

Human liver cancer cell line

PDL 1:

Programmed death Ligand-1

TAIII:

Timosaponin

A2780:

Cell line of ovarian cancer

GLUT-2:

Glucose Transporter 2

K562/ADR:

Myelogenous leukemia cell resistant to Adriamycin

GB:

Galbanic acid

TRAIL:

Tumour Necrosis factor-related apoptosis inducing ligand

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Acknowledgements

We want to acknowledge Dr. R.S. Gaud, Director, SVKM's NMIMS Deemed-to-be University, Shirpur Campus, for providing me with excellent research facilities and deep encouragement while pursuing this project. We would also like to acknowledge Prof. Ajazuddin, Associate Dean, School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 425405, India, for constant support.

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  1. Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM’S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India

    Disha Shah & Sankha Bhattacharya

  2. Department of Pharmaceutics, Rungta College of Pharmaceutical Sciences & Research, Khoka-Kurud Road, Bhilai, Chhattisgarh, 490024, India

    Ajazuddin

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  1. Disha Shah
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  2. Ajazuddin
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  3. Sankha Bhattacharya
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DS and SB were involved in the conception and design, or analysis and interpretation of the data; drafting of the paper, revising it critically for intellectual content; and Ajazuddin did final approval of the version to be published. DS, Ajazuddin and SB agree to be accountable for all aspects of the work.

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Correspondence to Sankha Bhattacharya.

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Shah, D., Ajazuddin & Bhattacharya, S. Role of natural P-gp inhibitor in the effective delivery for chemotherapeutic agents. J Cancer Res Clin Oncol 149, 367–391 (2023). https://doi.org/10.1007/s00432-022-04387-2

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