Anti-cancer Immune-modulatory Activities of Panax Genus Extracts and Bioactive Compounds

ABSTRACT

Cancer was ranked second cause of death by WHO in 2018. Surgery, radiotherapy, and chemotherapy individually or in combination are less effective when cancer has started its metastasis. Chemotherapy; a first line of therapy goes sometimes with fatal side-effects like killing normal fast-growing cells; a limitation of its use. Recently, immunotherapy has gained public attention. However, due to requirements in sophisticated equipment and intensive knowledge in other immunotherapy types, immune-modulation gained preference. Many natural bioactive compounds can work as immunomodulators. This paper collected immunomodulating activities of extracts and bioactive compounds of P. genus against cancer, providing a theoretical resource for ginseng-based anti-cancer immunotherapeutic research.

KEYWORDS:

• Ginsenosides
• anti-cancer
• immune system
• immune-modulation

Declaration of interest

Authors declare no conflict of interest.

List of abbreviations and acronyms

OH: Hydroxyl radical

5FU:5 Fluorouracil

Bcl-XL: B cell lymphoma-extra large

C: carbon

C-20: Carbon 20

C-3: Carbon 3

C-6: Carbon 6

cAMP: Cyclic adenosine monophosphate

CCL2: c-c motif ligand 2

CCL28:c-c motif ligand 28

CCl5: Chemokine ligand 5

CD8⁺ T: Cytotoxic T lymphocyte.

C-FLIP: Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein

CHK1: Checkpoint kinase 1gene

CHK2: Checkpoint kinase 1gene

Ck: Ginsenoside Compound K

ConA: Concanavalin A

CT26: a murine colorectal carcinoma cell line

CXCL1:Cxcl1 gene

CXCL10:C-X-C motif ligand 10

CXCL9:C-X-C motif ligand 9

DCs: Dendritic cells

DNA: Deoxy-ribonucleic acid

F1: Ginsenoside F1

FCγR Low affinity immunoglobulin gamma Fc region receptor III-A

FLT3L: FMS-like tyrosine kinase 3 ligand

GM-CSF: Granulocyte-macrophage colony-stimulating factor

GPS: Ginseng polysaccharide.

H2Ax: H2Ax gene

HIF-1a: Hypoxia-inducible factor 1-alpha

HOCl.: Hydrochloric radical.

IBD: Inflammatory Bowel Disease

IFN-γ Interferon Gamma

IL-1: Interleukin-1

IL-10: Interleukin-10

IL-12: Interleukin-12

IL-1α: Interleukin-1α

IL-23: Interleukin-23

IL-35: Interleukin-35

IL-6: Interleukin-6

iNOS: inducible nitric oxide synthase

IP-10: IFN-γinducible protein-10 (also CCL10)

JAK2/STAT3: Janus kinases-2 signal transducer and activator of transcription −3 pathway

LLC: Lewis lung carcinoma

LOX: Lysyl oxidase

LPS: Lipopolysaccahride

MCP-1: monocyte chemo-attractant protein-1 (also CCL2)

MCs: Mast cells.

MDSC: Myeloid-derived suppressor cells

MHC-1:Major Histocompatibility class 1

MHC-2: Major Histocompatibility class 2

MiR-146a: MicroRNA-146a

MMP-1: Matrix metalloproteinase-1

MMP-14: Matrix metalloproteinase-14

MMP-2: Matrix metalloproteinase-2

MMP-3: Matrix metalloproteinase-3

MMP-7: Matrix metalloproteinase-7

MMP-9: Matrix metalloproteinase-9

NADPH: Nicotinamide adenine dinucleotide phosphate

NFĸB: Nuclear factor kappa light chain enhancer of activated B cells

NK: Natural killer cells

O⁻²: Superoxide anion

OH: Hydroxyl

ONOO⁻: Peroxinitrite

P47 Phox: Neutrophile cytosol factor 1

P58 MAPK: P 58 mitogen activated protein kinase

P67 Phox: Neutrophil cytosol factor 2

PD-1: Programmed cell death protein-1

PDL-1: Programmed death-ligand 1

PGE2: Prostaglandin E2

PGHS-2: Prostaglandin G/H Synthase Isoenzyme 2

R6: Ginsenoside R6

Raw264.7: balb/c mice derived macrophage-like cell line

Rb1: Ginsenoside Rb1

Rb2: Ginsenoside Rb1

Rc: Ginsenoside Rbc

Rd: Ginsenoside Rd

Re: Ginsenoside Re

Rf: Ginsenoside Rf

Rg: Ginsenoside Rg

RG: Red ginseng

Rg1: Ginsenoside Rg1

Rg2: Ginsenoside Rg2

Rh: Ginsenoside Rh

Rh2: Ginsenoside Rh2

Rh3: Ginsenoside Rh3

RIP2: Receptor interacting protein kinase 2

RNA: Ribonucleic acid

ROS: Reactive Oxygen Species

RP1: Retinitis pigmentosa 1

STAT-3: Signal transducer and activator of transcription 3

TGF-α: Transforming growth factor-α

TGF-α ransforming growth factor-beta 1

TNF-α Tumor necrosis factor-α

uPa: Urokinase receptor

VEGF: Vascular endothelial growth factor.

WHO: World Health Organization

itric oxide.

Additional information

Funding

This work was supported by the “Đề án phát triển và ứng dụng công nghệ sinh học trong lĩnh vực công nghiệp chế biến” [DT.11.19/CNSHCB].