Abstract
In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280–320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm-2) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB-induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF-кB, TNF-α, IL-6, COX-2, VEGF, TGF-ß1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis.
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References
American Cancer Society. Cancer Facts & Figures 2015.
M. Saraiya, K. Glanz, P. A. Briss, P. Nichols and C. White, Interventions to prevent skin cancer by reducing exposure to ultraviolet radiation: A systematic review, Am. J. Prev. Med., 2004, 27(5), 422–466.
N. Ramachandran, N. Rajendra Prasad, K. V. Pugalendi and V. P. Menon, Modulation of UVB-induced oxidative stress by ursolic acid in human blood lymphocytes, Asian J. Biochem., 2008, 3(1), 11–18.
S. D. Sharma and S. K. Katiyar, Dietary grape seed proanthocyanidins inhibit UVB- induced cyclooxygenase-2 expression and other inflammatory mediators in UVB-exposed skin and skin tumors of SKH-1 hairless mice, Pharm. Res., 2010, 27, 1092–1102.
S. P. Divya, X. Wang, P. Pratheeshkumar, Y. O. Son, R. V. Roy, D. Kim, J. Dai, J. A. Hitron, L. Wang, A. Sha, X. Shi and Z. Zhang, Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-кB signaling pathways in SKH-1 mice skin, Toxicol. Appl. Pharmacol., 2015, 8, 13295–13303.
M. Rahman, J. K. Kundu, J. W. Shin, H. K. Na and Y. J. Surh, Docosahexaenoic Acid Inhibits UVB-Induced Activation of NF-kB and Expression of COX-2 and NOX-4 in HR-1 Hairless Mouse Skin by Blocking MSK1 Signaling, PLoS One, 2011, 6–11, e28065.
Y. J. Choi, Y. Uehara, J. Y. Park, S. J. Kim, S. R. Kim and H. W. Lee, et al., Mhy884, a newly synthesized tyrosinase inhibitor, suppresses UVB-induced activation of NF-кB signaling pathway through the down regulation of oxidative stress, Bioorg. Med. Chem. Lett., 2014, 24, 1344–1348.
M. Sumiyoshi, T. Hayashi and Y. Kimura, Effects of the non sugar fraction of brown sugar on chronic ultraviolet B irradiation-induced photo aging in melanin-possessing hairless mice, J. Nat. Med., 2009, 63, 130–136.
G. Ferrari, V. Terushkin, M. J. Wolff, X. Zhang, V. Cristina, P. Poggio, G. Pintucci and P. Mignatti, TGF-ß1 induces endothelial cell apoptosis by shifting VEGF activation OF p38MAPK from the prosurvival p38ß to pro-apoptotic p38a, Mol. Cancer Res., 2012, 10(5), 605–614.
X. P. Zhang, F. Liu and W. Wang, Interplay between Mdm2 and HIPK2 in the DNA damage response, J. R. Soc., Interface, 2014, 11(96), pii: 20140319.
G. A. Filip, I. D. Postescu, P. Bolfa, C. Catoi, A. Muresan and S. Clichici, Inhibition of UVB-induced skin phototoxicity by a grape seed extract as modulator of nitrosative stress, ERK/NF-kB signaling pathway and apoptosis, in SKH-1 mice, Food Chem. Toxicol., 2013, 57, 296–306.
F. Yogianti, M. Kunisada, R. Ono, K. Sakumi, Y. Nakabeppu and C. Nishigori, Skin tumors induced by narrowband UVB have higher frequency of p53 mutations than tumors induced by broadband UVB independent of Ogg1 genotype, Mutagenesis, 2012, 27(6), 637–643.
M. R. Farrukh, U. A. Nissar, P. J. Kaiser, Q. A. Praduman, R. Sharma, S. Bhushan, A. Sheikh Tasduq, Glycyrrhizic acid (GA) inhibits reactive oxygen Species mediated photodamage by blocking ER stress and MAPK pathway in UV-B irradiated human skin fibroblasts, J. Photochem. Photobiol., B, 2015, 148, 351–357.
B. H. Youn and H. J. Yang, Chemoprevention of skin cancer with dietary phytochemicals, skin cancer overview, ed. Y. Xi, In Tech., 2011, DOI: 10.5772/26706.
V. M. Linck, A. L. Silva, M. Figueiro, E. B. Carama, P. R. Moreno and E. Elisabetsky, Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice, Phytomedicine, 2010, 17, 679–683.
Q. Wu, L. Yub, J. Qiu, B. Shen, B. D. Wang, L. W. Soromou and H. Fenga, Linalool attenuates lung inflammation induced by Pasteurella multocida via activating Nrf-2 signaling pathway, Int. Immunopharmacol., 2014, 21, 456–463.
B. H. Cheng, L. Y. Sheenand and S. T. Chang, Evaluation of anxiolytic potency of essential oil and S-(+)-linalool from Cinnamomum osmophloeum ct. linalool leaves in mice, J. Tradit. Complement. Med., 2015, 5, 27–34.
J. M. Cherng, D. E. Shieh, W. Chaing, M. Y. Chang and L. C. Chiang, Chemopreventive effects of minor dietary constituents in common foods on human cancer cells, Biosci., Biotechnol., Biochem., 2007, 71, 1500–1504.
S. Jana, K. Patra, S. Sarkar, J. Jana, G. Mukherjee, S. Bhattacharjee and M. D. Prasad, Antitumorigenic Potential of Linalool Is Accompanied by Modulation of Oxidative Stress: An In Vivo Study in Sarcoma-180 Solid Tumor Model, Nutr. Cancer, 2014, 37, 1–14.
A. R. Koroch, H. R. Juliani and J. A. Zygadlo, Bioactivity of essential oils and their components, in Flavours and Fragrances, ed. R. G. Berger, Springer-Verlag, Berlin, Heidelberg, 2007, vol. 97, pp. 87–115.
M. Huo, X. Cui, J. Xue, G. Chi, R. Gao and X. Deng, Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model, J. Surg. Res., 2013, 180(1), 47–54.
A. Balupillai, N. R. Prasad, K. Ramasamy, G. Muthusamy, M. Shanmugham, K. Govindasamy and S. Gunaseelan, Caffeic acid inhibits UVB-induced inflammation and photocarcinogenesis through activation of peroxisome proliferator-activated receptor-γ in mouse skin, Photochem. Photobiol., 2015, 91(6), 1458–1468.
R. Agarwal, S. K. Katiyar, S. G. Khan and H. Mukhtar, Protection against ultraviolet-B radiation-induced effects in the skin of SKH-1 hairless mice by a polyphenolic fraction isolated from green tea, Photochem. Photobiol., 1993, 58, 695–700.
W. G. Niehaus and B. Samuelsson, Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation, Eur. J. Biochem., 1968, 6, 126–130.
P. Kakkar, B. Das and P. N. Viswanathan, A modified spectrophotometric assay of superoxide dismutase, Indian J. Biochem. Biophys., 1984, 21, 130–132.
A. K. Sinha, Colorimetric assay of catalase, Anal. Biochem., 1972, 47, 389–394.
J. T. Rotruck, A. L. Pope, H. E. Ganther, A. B. Swanson, D. G. Hafeman and W. G. Hoekstra, Selenium: Biochemical role as a component of glutathione peroxidase, Science, 1973, 179, 588–590.
A. L. M. Ivan, M. Z. Campanini, R. M. Martinez, V. S. Ferreira, V. S. Steffen, F. T. M. C. Vicentini, F. M. P. Vilela, F. S. Martins, A. C. Zarpelon, T. M. Cunha, M. J. V. Fonseca, M. M. Baracat, S. R. Georgetti, W. A. Verri and R. Casagrande, Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro, J. Photochem. Photobiol., B, 2014, 138, 124–133.
J. M. Page, A. R. Merkel, N. S. Ruppender, R. Guo, U. C. Dadwal, S. A. Cannonier, S. Basu and S. A. Guelcher, Matrix rigidity regulates the transition of tumor cells to a bonedestructive phenotype through integrin ß 3 and TGF-ß receptor type II, Biomaterials, 2015, 64, 33–44.
F. Ali and S. Sultana, Repeated short-term stress synergizes the ROS signalling through upregulation of NFkB and iNOS expression induced due to combined exposure of trichloroethylene and UVB rays, Mol. Cell. Biochem., 2012, 360, 133–145.
S. Rajput and A. Wilber, Roles of inflammation in cancer initiation, progression and metastasis, Front. Biosci., Scholar Ed., 2010, 2, 176–183.
G. Srithar, M. Sudha and N. Nalini, Linalool Exerts Dose Dependent Chemopreventive Effect against 1, 2-Dimethylhydrazine Induced Rat Colon Carcinogenesis, Int. J. Pharm. Biol. Sci. Arch., 2013, 4(4), 758–770.
J. W. Zhu, X. J. Wu, Z. F. Lu, D. Luo, S. Q. Cai and M. Zheng, Role of VEGF receptors in normal and psoriatic human keratinocytes: evidence from irradiation with different UV sources, PLoS One, 2013, 8(1), e55463.
Q. Hu, T. X. Shijun Zhao, W. D. Yuancheng, G. K. Chuanyu, X. Guowei and S. Periostin, Mediates TGF-ß-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells, Cell. Physiol. Biochem., 2015, 36, 799–809.
A. S. Pathania, S. K. Guru, M. K. Verma, C. Sharma, S. T. Abdullah, F. Malik, S. Chandra, M. Katoch and S. Bhushan, Disruption of the PI3K/AKT/mTOR signaling cascade and induction of apoptosis in HL-60 cells by an essential oil from Monarda citriodora, Food Chem. Toxicol., 2013, 62, 246–254.
B. Deepa and C. V. Anuradha, Effects of linalool on inflammation, matrix accumulation and podocyte loss in kidney of streptozotocin-induced diabetic rats, Toxicol. Mech. Methods, 2013, 23, 223–234.
H. Maeda, M. Yamazaki and Y. Katagata, Kuromoji (Lindera umbellate) Essential oil inhibits LPS- induced inflammation in RAW 264.7 Cells, Biosci., Biotechnol., Biochem., 2013, 77(3), 482–486.
Y. Gu, Z. Ting, X. Qiu, X. Zhang, X. Gan, Y. Fang, X. Xu and R. Xu, Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors, Toxicology, 2010, 268(1–2), 19–24.
A. Ziegler, A. S. Jonason, D. J. Leffell, J. A. Simon, H. W. Sharma, J. Kimmelman, L. Remington, T. Jacks and D. E. Brash, Sunburn and p53 in the onset of skin cancer, Nature, 1994, 372(6508), 773–776.
H. M. Gloster and D. G. Brodland, The epidemiology of skin cancer, Dermatol. Surg., 1996, 22(3), 217–226.
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Gunaseelan, S., Balupillai, A., Govindasamy, K. et al. The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice. Photochem Photobiol Sci 15, 851–860 (2016). https://doi.org/10.1039/c6pp00075d
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DOI: https://doi.org/10.1039/c6pp00075d