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Phytochemicals: Current Understandings of the Modern Therapeutic Approaches for Hepatocellular Carcinoma

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Phytochemicals Targeting Tumor Microenvironment in Gastrointestinal Cancers

Abstract

The growing occurrence of hepatocellular carcinoma (HCC) worldwide poses major concerns because of high mortality rate and poor prognosis. A lack of explicit diagnostics makes early detection of HCC implausible accentuating the demand of novel therapeutic approaches. In this chapter we discuss briefly major risk factors that contribute to the development of HCC and progress made in the identification of new molecular biomarkers and their significance in the detection of HCC. Here, our main focus is on recent advances made in the development of phytochemicals as novel prophylactics and therapeutic agents. First, we discuss a number of phytochemicals that are used to prevent or treat a variety of cancers. Subsequently, our emphasis is shifted on phytochemicals that are specifically significant in the treatment or prevention of HCC. A number of phytochemicals are emerging as plausible therapeutic agents for the treatment of HCC and are discussed in this chapter.

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Abbreviations

ABCG2:

Adenosine triphosphate (ATP)-binding cassette subfamily G member 2

ACVR1:

Activin A receptor type I

AFLD :

Alcoholic fatty liver disease

AFP:

Alpha fetoprotein

ALD:

Alcohol-related liver disease

ALT :

Alanine transaminase

AST:

Aspartate transaminase

Bcl-2:

B-cell lymphoma 2

BMP:

Bone morphogenetic protein

CD8+ T cell:

Cluster of differentiation 8 T cell

COX-2:

Cyclooxygenase-2

CRAE :

C. rhizome aqueous extract

CSC:

Cancer stem cell

CT:

Computed tomography

CTL-4:

Cytotoxic T-lymphocyte-associated protein 4

CXCL1:

Chemokine (C-X-C motif) ligand 1

CXCR4:

C-X-C motif chemokine receptor 4

DIHS :

Drug-induced hepatic steatosis

DLK-1:

Delta-like 1/fetal antigen-1

DNA:

Deoxyribonucleic acid

EGCG :

Epigallocatechin-3-gallate

EMT:

Epithelial-mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

GLB1:

Galactosidase beta 1

GSTM1:

Glutathione S-transferase mu 1

GSTT1 :

Glutathione S-transferase theta 1

GTP:

Guanosine-5′-triphosphate

HA:

Hyaluronic acid

HAV:

Hepatitis A virus

HBeAg:

Hepatitis B e-antigen

HBV:

Hepatitis B virus

HBx:

HBV-encoded X antigen

HCC:

Hepatocellular carcinoma

hCSC:

Human CSC

HCT-15:

Human colorectal adenocarcinoma

HCV:

Hepatitis C virus

HLA:

Human leukocyte antigen

HPC:

HCC progenitor cell

Hsp:

Heat-shock protein

IBD:

Inflammatory bowel disease

IGF :

Insulin-like growth factor 1

IKK:

IκB kinase

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

JAK2:

Janus kinase 2

JNK:

c-Jun N-terminal kinase

LGR5:

Leucine-rich repeat-containing G-protein-coupled receptor 5

MAPK:

Microtubule-associated protein kinase

MCF-7:

Michigan Cancer Foundation-7

MDM2:

Mouse double minute 2 homolog

miRNA:

microRNA

MKK7:

Mitogen-activated protein kinase kinase 7

MRA:

Magnetic resonance angiogram

MRI:

Magnetic resonance imaging

mTOR:

Mammalian target of rapamycin

NAFLD :

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

NF-kB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

OCT4:

Octamer-binding transcription factor 4

PAE:

Prostate artery embolization

PARP:

Poly-ADP-ribose polymerase

PD-1:

Programmed cell death protein 1

PDGF-BB :

Platelet-derived growth factor subunit BB

PDL-1:

Programmed death ligand-1

PI3K:

Phosphoinositide 3-kinase

PKB:

Protein kinase B

PKC:

Protein kinase C

PPAR:

Peroxisome proliferator-activated receptor

PTEN:

Phosphatase and tensin homolog

RNA :

Ribonucleic acid

ROCK:

Rho-associated protein kinase

ROS:

Reactive oxygen species

SMAD7:

Mothers against Dpp homolog 8

SNP:

Single-nucleotide polymorphism

STAT3:

Signal transducer and activator of transcription 3

STRAP:

Serine/threonine kinase receptor-associated protein

T2DM :

Type 2 diabetes

TACE:

Transarterial chemoembolization

TAE:

Transarterial embolization

TCTP:

Translationally controlled tumor protein

TERT:

Telomerase reverse transcriptase

TGF-β1:

Transforming growth factor-beta 1

TGP :

Total glucosides of peony

TIPRL:

TOR signaling pathway regulator

TNFα:

Tumor necrosis factor alpha

TRAIL :

TNF-related apoptosis-inducing ligand

VEGF:

Vascular endothelial growth factor

XRCC3 :

X-ray repair cross complementing 3

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Acknowledgement

This work was supported by NIH’s R01-DK81413 (to SAS) from the National Institute of Diabetes and Digestive and Kidney Diseases and by the UCF Reach for the Stars Award (to SAS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.

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  1. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA

    Austin Cook & Shadab A. Siddiqi

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  1. Austin Cook
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  2. Shadab A. Siddiqi
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Correspondence to Shadab A. Siddiqi .

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  1. Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

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Cook, A., Siddiqi, S.A. (2020). Phytochemicals: Current Understandings of the Modern Therapeutic Approaches for Hepatocellular Carcinoma. In: Nagaraju, G.P. (eds) Phytochemicals Targeting Tumor Microenvironment in Gastrointestinal Cancers. Springer, Cham. https://doi.org/10.1007/978-3-030-48405-7_14

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