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Greasing the Wheels of Pharmacotherapy for Colorectal Cancer: the Role of Natural Polyphenols

  • REVIEW
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Abstract

Purpose of Review

The main purpose of this review, mainly based on preclinical studies, is to summarize the pharmacological and biochemical evidence regarding natural polyphenols against colorectal cancer and highlight areas that require future research.

Recent Findings

Typically, colorectal cancer is a potentially preventable and curable cancer arising from benign precancerous polyps found in the colon’s inner lining. Colorectal cancer is the third most common cancer, with a lifetime risk of approximately 4 to 5%. Genetic background and environmental factors play major roles in the pathogenesis of colorectal cancer. Theoretically, a multistep process of colorectal carcinogenesis provides enough time for anti-tumor pharmacotherapy of colorectal cancer. Chronic colonic inflammation, oxidative stress, and gut microbiota imbalance have been found to increase the risk for colorectal cancer development by creating genotoxic stress within the intestinal environment to generate genetic mutations and epigenetic modifications. Currently, numerous natural polyphenols have shown anti-tumor properties against colorectal cancer in preclinical research, especially in colorectal cancer cell lines.

Summary

In this review, the current literature regarding the etiology and epidemiology of colorectal cancer is briefly outlined. We highlight the findings of natural polyphenols in colorectal cancer from in vitro and in vivo studies. The scarcity of human trials data undermines the clinical use of natural polyphenols as anti-colorectal cancer agents, which should be undertaken in the future.

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Data Availability

The data that support the findings of this study are available from the corresponding author, Chengu Niu, upon reasonable request.

Abbreviations

5-mC :

5-Methylcytosine

ACF :

Aberrant crypt foci

AOM :

Azoxymethane

APC :

Adenomatous polyposis coli

BAX :

Bcl-2-associated X protein

BRAF :

B type Raf kinase

CIMP :

CpG island methylator phenotype

CIN :

Chromosomal instability

DMH :

1,2-Dimethylhydrazine

CRC :

Colorectal cancer

DSS,:

Dextran sodium sulfate

ERK :

Extracellular signal-regulated kinases

GDP :

Guanosine diphosphate

GTP :

Guanosine triphosphate

HIF-1α :

Hypoxia inducible factor-1α

KRAS :

Kirsten rat sarcoma

mTOR :

Mechanistic target of rapamycin

MEK :

Mitogen-activated protein kinase kinase

MMR :

Mismatch repair

MSI :

Microsatellite instability

NF-κB :

Nuclear factor-κB

PI3K :

Phosphatidylinositol-3-kinase

RAF :

Rapidly accelerated fibrosarcoma

RAGE :

Receptor for advanced glycosylation end products

RAS :

Rat sarcoma

ROS :

Reactive oxygen species

SSL :

Sessile serrated lesions

STAT3 :

Signal transducer and activator of transcription 3

TGF-β RII :

Transforming growth factor -beta type II receptors

TLR4 :

Toll-like receptor 4

TNF-α :

Tumor necrosis factors α

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Authors and Affiliations

  1. Internal Medicine Residency Program, Rochester General Hospital, Rochester, NY, 14621, USA

    Chengu Niu

  2. Rainier Springs Behavioral Health Hospital, Vancouver, 98686, USA

    Jing Zhang

  3. Division of Gastroenterology, Rochester General Hospital, Rochester, NY, 14621, USA

    Patrick Okolo

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  1. Chengu Niu
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  2. Jing Zhang
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All authors contributed to the study conception and design. Patrick I Okolo Iii critically revisedthe manuscript and provided feedback. Chengu Niu and Jing Zhang reviewed the literature and drafted the manuscript;Chengu Niu generated the figure artwork. All authors read and approved the final manuscript.

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Niu, C., Zhang, J. & Okolo, P. Greasing the Wheels of Pharmacotherapy for Colorectal Cancer: the Role of Natural Polyphenols. Curr Nutr Rep 12, 662–678 (2023). https://doi.org/10.1007/s13668-023-00512-w

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