The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment
Abstract
:1. Introduction
2. Anti-Carcinogenic/Chemopreventive Effect of Eugenol and Its Relation to the Inhibition of Oxidative Stress
3. Cytotoxic and Antitumor Effects of Eugenol and Its Relation to the Induction of Oxidative Stress
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
Apaf-1 | Apoptotic protease activating factor 1 |
Bax | BCL2 associated X, apoptosis regulator |
Bcl-2 | B-cell lymphoma 2, apopstosis regulator |
COX-2 | Cyclooxygenase-2 |
CYP 1A1 | Cytochrome P450 family 1 subfamily A member 1 |
CYP1B1 | Cytochrome P450 family 1 subfamily B member 1 |
DFF45 | DNA fragmentation factor 45 |
DMBA | 7,12-dimethylbenz[a]anthracene |
DNA | Deoxyribonucleic acid |
DPPH | 2,2-diphenyl-1-picrylhydrazyl |
ER | Endoplasmic reticulum |
Gadd45 | Growth arrest and DNA damage-inducible 45 |
IC50 | Half maximal inhibitory concentration |
IKKβ | Inhibitor of kappa B |
IL-6 | Interleukin-6 |
iNOS | Inducible nitric oxide synthase |
IκBα | IκB Kinase α |
MA | Malonaldehyde |
MCF 10A-ras | H-ras transfected MCF 10A |
MMP | Matrix metalloproteinases |
MNNG | N-Methyl-N′-nitro-N-nitrosoguanidine |
NF-κB | Nuclear factor kappa B |
PARP | Poly(ADP-ribose)polymerase |
PCNA | Proliferating cell nuclear antigen |
PGE2 | Prostaglandin E2 |
RECK | Reversion-inducing-cysteine-rich protein with kazal motifs |
ROS | Reactive Oxygen Species |
SGOT | Serum glutamic-oxaloacetic transaminase |
TA | Thioacetamide |
TBARS | Thiobarbituric acid-reactive substances |
TIMP-2 | Tissue inhibitor of metalloproteinase-2 |
TNF-α | Tumor necrosis factor alpha |
TPA | 12-otetradecanoylphorbol-13-acetate |
VEGF | Vascular endothelial growth factor |
VEGFR1 | Vascular endothelial growth factor receptor 1 |
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Carcinogenesis Model | Carcinogen | Eugenol Administration | Effect | References |
---|---|---|---|---|
Skin carcinogenesis | DMBA + TPA | Topical | Reduction in tumor incidence and size; and/or development of papillomatous keratoacanthoma with minimal cell proliferation but without squamous cell carcinoma | [20] |
Skin carcinogenesis | DMBA + croton oil | Topical | Inhibition of tumor formation ~60% | [21,22] |
Skin carcinogenesis | benzo[a]pyrene | Topical | Inhibition of tumor formation ~50% | [23] |
Skin Carcinogenesis | DMBA | Topical | Minimal protection | [24] |
Gastric carcinogenesis | MNNG | Intragastric | Inhibition of tumor formation ~75% | [25,26] |
Lung carcinogenesis | Urethane | Oral | No protection | [28] |
Cell Lines | Histological Type | Origin | IC50 (µM) | References |
---|---|---|---|---|
Cancer cells | ||||
Sbcl2 | Primary melanoma | Human | ~0.5 | [45] |
WM3211 | Primary melanoma | Human | ~0.5 | [45] |
WM98-1 | Primary melanoma | Human | ~0.5 | [45] |
WM1205Lu | Metastatic melanoma | Human | ~0.5 | [45] |
SK-Mel-28 | Melanoma | Human | 7.2 | [51] |
A2058 | Melanoma | Human | 12.2 | [51] |
WM266-4 | Melanoma | Human | >100 | [64] |
SK-Mel-28 | Melanoma | Human | >100 | [64] |
LCP-Mel | Melanoma | Human | >100 | [64] |
LCM-Mel | Melanoma | Human | >100 | [64] |
PNP-Mel | Melanoma | Human | >100 | [64] |
CN-MelA | Melanoma | Human | >100 | [64] |
13443 | Melanoma | Human | >100 | [64] |
GR-Mel | Melanoma | Human | >100 | [64] |
HSG | Submandibular gland adenocarcinoma | Human | ~100 | [59] |
396 | [60] | |||
T47-D | Breast carcinoma | Human | 0.9 | [50] |
MDA-MB-231 | Breast adenocarcinoma | Human | 1.7 | [50] |
15.1 | [51] | |||
~1600 | [71] | |||
MCF-7 | Breast adenocarcinoma | Human | 1.5 | [50] |
22.8 | [51] | |||
~400 | [70] | |||
900 | [71] | |||
HCT-15 | Colon adenocarcinoma | Human | 300 | [69] |
HT-29 | Colon adenocarcinoma | Human | 500 | [69] |
Caco-2 | Colon carcinoma | Human | ~750 | [73] |
SNU-C5 | Colon carcinoma | Human | 129.4 | [46] |
LNCaP | Prostate adenocarcinoma | Human | ~550 | [49] |
PC-3 | Prostate carcinoma | Human | ~180 | [49] |
DU-145 | Prostate carcinoma | Human | 30.4 | [48] |
SIHA | Cervical carcinoma | Human | 18.3 | [51] |
HeLa | Cervical carcinoma | Human | 500 | [72] |
HepG2 | Hepatocellular carcinoma | Human | 118.6 | [46] |
~500 | [73] | |||
3LL | Lewis lung carcinoma | Mouse | 89.6 | [46] |
KB | Oral squamous cell carcinoma | Human | 28.5 | [48] |
HSC-2 | Oral squamous cell carcinoma | Human | ~700 | [72] |
HOS | Osteosarcoma | Human | 1500 | [66] |
HL-60 | Promyelocytic leukemia | Human | 23.7 | [46] |
380 | [61] | |||
U-937 | Histocytic lymphoma | Human | 39.4 | [46] |
Non-cancer cells | ||||
MCF 10A | Breast epithelial | Human | 2.2 | [50] |
Tumor | Histological Type | Origin | Dose (mg/kg) | Treatment | Route | Inhibition Rate (%) | References |
---|---|---|---|---|---|---|---|
B16 | Melanoma | Mouse | 125 | Twice a week | i.p. | 62 | [45] |
Ehrlich (ascites model) | Carcinoma | Mouse | 100 | Every two days for four weeks | i.p. | 28.9 | [74] |
Ehrlich (solid model) | Carcinoma | Mouse | 100 | Every two days for four weeks | i.p. | 24.4 | [74] |
MDA-MB-231 | Breast adenocarcinoma | Human | 100 | Every two days for four weeks | i.p. | ~66 | [50] |
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Bezerra, D.P.; Militão, G.C.G.; De Morais, M.C.; De Sousa, D.P. The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment. Nutrients 2017, 9, 1367. https://doi.org/10.3390/nu9121367
Bezerra DP, Militão GCG, De Morais MC, De Sousa DP. The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment. Nutrients. 2017; 9(12):1367. https://doi.org/10.3390/nu9121367
Chicago/Turabian StyleBezerra, Daniel Pereira, Gardenia Carmen Gadelha Militão, Mayara Castro De Morais, and Damião Pergentino De Sousa. 2017. "The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment" Nutrients 9, no. 12: 1367. https://doi.org/10.3390/nu9121367