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Role of Capsaicin in Oxidative Stress and Cancer pp 19–46Cite as

Role of Death Receptors Belonging to the TNF Family in Capsaicin-Induced Apoptosis of Tumor Cells

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Part of the book series: Diet and Cancer ((DICA,volume 3))

Abstract

Capsaicin has been shown to induce apoptosis in various transformed cell types in vitro and in vivo. Apoptosis is triggered by an induction phase that is highly dependent on cell type and apoptogenic stimuli (e.g., death receptors, oxidative stress, DNA damage, ion fluctuations, and cytokines). This is followed by an effector phase where the cell undergo distinct biochemical changes as results of intrinsic mitochondrial-dependent and/or extrinsic death receptor-mediated apoptotic pathways. Depending on the concentration, duration of exposure and route of administration, CPS may either induce apoptosis in different cell types in a TRPV1-dependent and independent manner. It is generally accepted that CPS-mediated apoptosis is manifested by reactive oxygen species (ROS) generation, elevations in [Ca2+]i and mitochondrial transmembrane potential dissipation. However recent reports, indicate the ability of CPS to induce also up-regulation of Fas/CD95, TRAIL-R1/DR4, TRAIL-R2/DR5 and TNF-R1/DR1 death receptor expression, Fas Ligand-independent Fas-dependent TRPV1-mediated apoptosis of cancer cells, or to sensitize tumor cells to TRAIL-induced apoptosis. Unraveling the molecular mechanisms that underlie the CPS-induced targeting of death receptor in tumor cells and the death intracellular pathways activated by capsaicin, could provide the basis for novel therapeutic strategies in cancer patients.

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Abbreviations

[Ca2+]i :

Intracellular free Ca2+

AEA:

Anandamide

AFT3:

Activating transcription factor 3

AKT:

V-akt murine thymoma viral oncogene homolog

AP-1:

Activator protein 1

APRIL:

A PRoliferation Inducing Ligand

ATM:

Ataxia telangiectasia mutated

ATP:

Adenosine triphosphate

BAFF:

B-cell activating factor (BAFF)

BAX:

The Bcl-2–associated X protein

Bcl-2:

B-cell lymphoma 2

Bcl-XL :

Bcl-2-like protein 1

Bid:

BH3 interacting domain death agonist

C/EBPβ:

CCAAT/enhancer binding protein β

CaM:

Ca2+/calmodulin-dependent protein

CFLAR:

CASP8 and FADD-like apoptosis regulator

CHOP:

C/EBP homology protein

COXs:

Cyclooxygenases

CPS:

Capsaicin

c-Src:

Sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog

CyT C:

Cytochrome C

DAXX:

Death Associated Protein

DD:

Death domain

DED:

Death effector domain

DISC:

Death-inducing signaling complex

DR:

Death receptors

DRG:

Dorsal root ganglion

EDAR:

Ectodysplasin A receptor

FADD:

Fas-associated death domain

FAF1:

Fas-associated factor 1

FAF-1:

FAS-associated factor 1

FAP-1:

Fas-associated phosphatase 1

FASL:

FAS ligand

FASL:

Fas ligand

FLASH:

FLICE - associated huge protein

FLICE:

FADD-like interleukin-1 beta-converting enzyme

FLIP:

FLICE inhibitory protein

GADD153:

DNA-damage-inducible transcript 3

GADD45:

DNA-damage-inducible 45 alpha

GRP78:

78 kDa glucose-regulated protein

GSK3β:

Glycogen synthase kinase 3 β

HER:

Human epidermal growth factor receptor

IAP:

Inhibitors of Apoptosis

IKK:

IκB kinase inhibitor

IRE 1:

Internal ribosome entry site

IκB:

Inhibitor of NF-κB

JNK:

c-Jun N-terminal protein kinase

MAPK:

Mitogen-activating protein kinase

MAPK:

Mitogen activated Protein Kinase

MDM2:

Murine double minute protein

MYC:

Myelocytomatosis viral oncogene homolog

NADH:

Nicotinamide adenine dinucleotide

NAG1:

Growth differentiation factor 15

NF-κB:

Nuclear factor kappa B

NGF:

Nerve Growth Factor

PIP2:

Phosphatidylinositol 4,5-bisphosphate

PMOR:

Plasma membrane oxidoreductase

RANK:

Receptor Activator for Nuclear Factor κ B Ligand

RIP:

Receptor interacting protein

RIP:

Receptor-interacting protein

RIPK2:

Receptor-interacting serine/threonine-protein kinase 2

ROS:

Reactive oxygen species

RTX:

Resinferatoxin

STAT 3:

Signal transducer and activator of transcription

TNF:

Tumor necrosis factor

TNFRs:

TNF receptors

TRADD:

TNFR-associated death domain

TRAF:

Tumor Necrosis Factor (TNF) receptor-associated factors

TRAFs:

TNF receptor associate factors

TRAIL:

TNF related apoptosis induced ligand

TRP:

Transient receptor potential

TRPV1:

Transient receptor potential vanilloid type-1

UC:

Urothelial cancer

WAF-1:

Cyclin-dependent kinase inhibitor 1

ΔΨ(m):

Mitochondrial membrane potential

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  1. School of Pharmacy, Section of Experimental Medicine, University of Camerino, Via Madonna delle Carceri 9, Camerino, MC, 62032, Italy

    Giorgio Santoni Ph.D., Sara Caprodossi, Valerio Farfariello, Sonia Liberati & Consuelo Amantini

  2. Department of Molecular Medicine, Sapienza University, 00100, Rome, Italy

    Sara Caprodossi & Sonia Liberati

  3. Department of Urology and Andrology, University of Perugia, Perugia, Italy

    Valerio Farfariello

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  1. Giorgio Santoni Ph.D.
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Santoni, G., Caprodossi, S., Farfariello, V., Liberati, S., Amantini, C. (2013). Role of Death Receptors Belonging to the TNF Family in Capsaicin-Induced Apoptosis of Tumor Cells. In: Srivastava, S. (eds) Role of Capsaicin in Oxidative Stress and Cancer. Diet and Cancer, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6317-3_2

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