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NF-κB in cancer therapy

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Abstract

The transcription factor nuclear factor kappa B (NF-κB) has attracted increasing attention in the field of cancer research from last few decades. Aberrant activation of this transcription factor is frequently encountered in a variety of solid tumors and hematological malignancies. NF-κB family members and their regulated genes have been linked to malignant transformation, tumor cell proliferation, survival, angiogenesis, invasion/metastasis, and therapeutic resistance. In this review, we highlight the diverse molecular mechanism(s) by which the NF-κB pathway is constitutively activated in different types of human cancers, and the potential role of various oncogenic genes regulated by this transcription factor  in cancer development and progression. Additionally, various pharmacological approaches employed to target the deregulated NF-κB signaling pathway, and their possible therapeutic potential in cancer therapy is also discussed briefly.

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Abbreviations

NF-κB:

Nuclear factor kappa B

IκBα:

Inhibitor of kappa B-α

IKK:

IκB kinase

NIK:

NF-κB-inducing kinase

TNF:

Tumor necrosis factor

LPS:

Lipopolysaccharide

TNFR:

TNF receptor

TLR:

Toll-like receptor

IL-1:

Interleukin-1

TCR:

T-cell receptor

TRAF:

TNFR-associated factor

RIP:

Receptor-interacting protein

TAK1:

TGF-β-activated kinase 1

BAFF:

B-cell-activating factor

HCC:

Hepatocellular carcinoma

PI3K:

PI3-kinase

HGF:

Hepatocyte growth factor

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

NS5A:

Non-structural 5A

IκBα-SR:

IκBα super-repressor

DEN:

Diethylnitrosamine

CAC:

Colitis-associated colon cancer

PRR:

Pattern recognition receptors

CK2:

Casein kinase 2

siRNA:

Small interfering RNA

ER:

Estrogen receptor

EGFR:

Epidermal growth factor receptor

RANK:

Receptor activator of NF-κB

IκBαM:

IκBα mutant

HNSCC:

Head and neck squamous cell carcinoma

HPV:

Human papillomavirus

DLBCL:

Diffuse large B-cell lymphoma

CLL:

Chronic lymphocytic leukemia

HL:

Hodgkin’s lymphoma

ATL:

Adult T-cell leukemia

HTLV-1:

Human T-cell leukemia virus type 1

EBV:

Epstein–Barr virus

CML:

Chronic myelogenous leukemia

ALL:

Acute lymphoblastic leukemia

ABC:

Activated B-cell-like

VEGF:

Vascular endothelial growth factor

PGHS:

Prostaglandin endoperoxide H synthases

COX:

Cyclooxygenase

AP-1:

Activator protein-1

PKC:

Protein kinase C

Rb:

Retinoblastoma

IAP:

Inhibitors of apoptosis

PMA:

Phorbol myristol acetate

MMP:

Matrix metalloproteinase

ECM:

Extracellular matrix

ELAM-1:

Endothelial-leukocyte adhesion molecule-1

VCAM-1:

Vascular cell adhesion molecule-1

ICAM-1:

Intercellular adhesion molecule-1

EMT:

Epithelial–mesenchymal transition

CXCR4:

CXC-chemokine receptor 4

MEKK1:

Mitogen-activated protein kinase/ERK kinase kinase

GSK-3β:

Glycogen synthase kinase-3 beta

PDK1:

Phosphoinositide-dependent protein kinase-1

MAP3K:

Mitogen-activated protein kinase kinase kinase

TBK1:

TANK-binding kinase 1

JNK:

c-Jun NH2-terminal kinase

MnSOD:

Manganese superoxide dismutase

FHC:

Ferritin heavy chain

ROS:

Reactive oxygen species

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

STAT3:

Signal transducer and activator of transcription 3

C/EBPβ:

CCAAT/enhancer-binding protein beta

HIF-1α:

Hypoxia-inducible transcription factor-1 alpha

NSAID:

Nonsteroidal anti-inflammatory drug

UPS:

Ubiquitin proteasome system

EGCG:

Epigallocatechin-3-gallate

ATO:

Arsenic trioxide

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Acknowledgments

This work was supported by NUHS Bench-to-Bedside grant to GS. Deanship of Scientific Research, College of Science Research Centre, King Saud University, Kingdom of Saudi Arabia, is also acknowledged. GS also thanks King Saud University, Riyadh, Kingdom of Saudi Arabia, for the Visiting Professorship. APK was supported by Grants from Singapore Ministry of Education Tier 2 [MOE2012-T2-2-139], Academic Research Fund Tier 1 [R-184-000-228-112], and Cancer Science Institute of Singapore, Experimental Therapeutics I Program [Grant R-713-001-011-271]. KSA was supported by the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korean Ministry of Education, Science and Technology (MoEST) (No. 2011-0006220).

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Authors and Affiliations

  1. Department of Pharmacology, Yong Loo Lin School of Medicine, Cancer Science Institute, National University of Singapore, Singapore, 117597, Singapore

    Feng Li, Jingwen Zhang, Alan Prem Kumar & Gautam Sethi

  2. School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Perth, WA, 6009, Australia

    Frank Arfuso, Alan Prem Kumar & Gautam Sethi

  3. Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia

    Arunachalam Chinnathambi, M. E. Zayed, Sulaiman Ali Alharbi & Gautam Sethi

  4. Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore, 117599, Singapore

    Alan Prem Kumar

  5. Department of Biological Sciences, University of North Texas, Denton, TX, 76203, USA

    Alan Prem Kumar

  6. Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, 1 Hoegi-Dong Dongdaemun-Gu, Seoul, 130-701, Republic of Korea

    Kwang Seok Ahn

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  1. Feng Li
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Li, F., Zhang, J., Arfuso, F. et al. NF-κB in cancer therapy. Arch Toxicol 89, 711–731 (2015). https://doi.org/10.1007/s00204-015-1470-4

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