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An Update on Potential Molecular Biomarkers of Dietary Phytochemicals Targeting Lung Cancer Interception and Prevention

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Abstract

Since ancient times, dietary phytochemicals are known for their medicinal properties. They are broadly classified into polyphenols, terpenoids, alkaloids, phytosterols, and organosulfur compounds. Currently, there is considerable interest in their potential health effects against various diseases, including lung cancer. Lung cancer is the leading cause of cancer deaths with an average of five-year survival rate of lung cancer patients limited to just 14%. Identifying potential early molecular biomarkers of pre-malignant lung cancer cells may provide a strong basis to develop early cancer detection and interception methods. In this review, we will discuss molecular changes, including genetic alterations, inflammation, signal transduction pathways, redox imbalance, epigenetic and proteomic signatures associated with initiation and progression of lung carcinoma. We will also highlight molecular targets of phytochemicals during lung cancer development. These targets mainly consist of cellular signaling pathways, epigenetic regulators and metabolic reprogramming. With growing interest in natural products research, translation of these compounds into new cancer prevention approaches to medical care will be urgently needed. In this context, we will also discuss the overall pharmacokinetic challenges of phytochemicals in translating to humans. Lastly, we will discuss clinical trials of phytochemicals in lung cancer patients.

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Abbreviations

AKT:

Protein kinase B

AMPK:

AMP activated protein kinase

ARE:

Antioxidant response element

B(a)P:

Benzo(a)pyrene

Bax:

Bcl-2 Associated X-protein

BPDE:

Benzo[a]pyrene diol epoxide

CCND1:

Cyclin D1

CD:

Conjugated dienes

CDK:

Cyclin dependent kinase

CIC:

Cancer initiating cells

Cmax:

Maximum plasma concentration

COX-2:

Cyclooxygenase 2

CREB:

CAMP-response element binding protein

CpG:

Cytosine phosphate guanine

DNMT:

DNA methyltransferase

DUSP5:

Dual Specificity Phosphatase 5

EGCG:

Epigallocatechin-3-gallate

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-to-mesenchymal transition

ENO1:

Enolase 1

EP4:

E-type prostanoid receptor 4

ER:

Estrogen receptor

ERK:

Extracellular signal-regulated kinase

GFR:

Growth factor receptor

GLS:

Glutaminase

GLUT1:

Glucose transporter type 1

GPCR:

G protein-coupled receptor

GPX:

Glutathione peroxidase

GSH:

Glutathione

GST:

Glutathione-s-tranferase

HDAC:

Histone deacetylase

HIF1A:

Hypoxia-inducible factor 1-alpha

HK2:

Hexokinases II

4-HNE:

4-Hydroxynonenal

IDH1:

Isocitrate dehydrogenase 1

IDH2:

Isocitrate dehydrogenase 2

I3C:

Indole-3-carbinol

IL1B:

Interleukin1B

IL6:

Interleukin6

IL8:

Interleukin8

JNK:

C-Jun N-terminal kinase

KEAP1:

Kelch-like ECH-associated protein 1

KRAS:

Kirsten rat sarcoma

LDH:

Lactate dehydrogenase

LLC:

Lewis lung carcinoma

lncRNAs:

Long noncoding RNAs

MAPK:

Mitogen activated protein kinase

MDA:

Malonyldialdehyde

MMP:

Matrix mellanoproteinase

mTOR:

Mechanistic target of rapamycin kinase

NF-κB:

Nuclear factor kappa B

NSCLC:

Non-small cell lung cancer

NOX:

NADPH oxidase

NRF2:

Nuclear factor erythroid 2-related factor 2

OSI:

Oxidative stress index

OXPHOS:

Oxidative phosphorylation

PARP:

Poly [ADP-ribose] polymerase

PGDH:

3-Phosphoglycerate dehydrogenase

PGE2:

Prostaglandin E synthase 2

PI3K:

Phosphatidylinositol-3-kinase

PIK3CA:

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha

PKM2:

Pyruvate kinase M2

PNS:

Panax notoginseng saponins

PTEN:

Phosphatase and tensin homolog

RAF:

Rapidly accelerated fibrosarcoma

RAR:

Retinoic acid receptor

RAS:

Rat sarcoma virus

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RTK:

Receptor tyrosine kinase

SAM:

S-adenosylmethionine

SCLC:

Small cell lung cancer

SIRT:

Sirtuin

SOD:

Superoxide dismutase

SP1:

Specificity protein 1

STAT3:

Signal transducer and activator of transcription 3

SWI/SNF:

SWItch/Sucrose Non-Fermentable

TAS:

Total antioxidant status

TKI:

Tyrosine kinase inhibitor

TNF:

Tumor necrosis factor

TOS:

Total oxidant status

Tp53:

Tumor protein 53

TSG:

Tumor suppressor gene

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Acknowledgements

We thank all the members of Professor Ah-Ng Tony Kong’s laboratory for their invaluable discussion and contribution in the preparation of this manuscript. Supported in part by Institutional funds and by NIH grant P30 ES005022.

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  1. Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    Rebecca Mary Peter, Pochung Jordan Chou, Ahmad Shannar, Komal Patel, Yuxin Pan, Parv Dushyant Dave & Jiawei Xu

  2. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    Rebecca Mary Peter, Pochung Jordan Chou, Ahmad Shannar, Yuxin Pan, Parv Dushyant Dave, Jiawei Xu, Md. Shahid Sarwar & Ah-Ng Tony Kong

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Peter, R.M., Chou, P.J., Shannar, A. et al. An Update on Potential Molecular Biomarkers of Dietary Phytochemicals Targeting Lung Cancer Interception and Prevention. Pharm Res 40, 2699–2714 (2023). https://doi.org/10.1007/s11095-023-03595-w

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