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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Insight into Mechanistic Action of Thymoquinone Induced Melanogenesis in Cultured Melanocytes

Author(s): Kamal U. Zaidi*, Firoz N. Khan, Sharique A. Ali and Kausar P. Khan

Volume 26, Issue 12, 2019

Page: [910 - 918] Pages: 9

DOI: 10.2174/0929866526666190506114604

Price: $65

Abstract

Background: Melanin plays a crucial role in camouflage, social communication and protection against harmful ultraviolet radiations. Melanin is synthesized by melanocytes through melanogenesis and several intrinsic and extrinsic factors are involved during the process. Any change occuring in the normal melanogenesis process can cause severe pigmentation problems of hypopigmentation or hyperpigmentation.

Objective: The present study is based on the evaluation of the effect of thymoquinone on melanogenesis and their possible mechanism of action using the B16F10 melanoma cell line for the production via blocking signaling pathways.

Methods: Phase contrast microscopy, cell viability, tyrosinase activity, melanin content and western blot analysis were used in the present study.

Results: In the present investigation, cultured melanocytes exhibit that the stimulation of melanin synthesis when treated with thymoquinone. Tyrosinase activity and melanin production in B16F10 melanoma cell line was increased in doze-dependent manner. In western blot, we investigated the involvement of the cAMP/PKA pathway in thymoquinone induced melanogenesis. It was observed protein kinase inhibitors PKA, PKC, PKB and MEK1 decreased the stimulatory effects of thymoquinone from 11.45- fold value to 8.312, 6.631, 4.51, and 7.211-fold value, respectively. However, the results also prove that thymoquinone may partially induce tyrosinase expression via PKA, PKB, PKC and MEK1 signaling pathways.

Conclusion: The present finding proposed that thymoquinone is a protective challenger for melanogenesis and it might be useful for the treatment of hypopigmentary disorders.

Keywords: Melanin, vitiligo, pathways, tyrosinase, melanoma, pigmentation.

Graphical Abstract

[1]
Lin, J.Y.; Fisher, D.E. Melanocyte biology and skin pigmentation. Nature, 2007, 445(7130), 843-850.
[http://dx.doi.org/10.1038/nature05660] [PMID: 17314970]
[2]
Brenner, M.; Hearing, V.J. The protective role of melanin against UV damage in human skin. Photochem. Photobiol., 2008, 84(3), 539-549.
[http://dx.doi.org/10.1111/j.1751-1097.2007.00226.x] [PMID: 18435612]
[3]
Ndiaye, M.A.; Nihal, M.; Wood, G.S.; Ahmad, N. Skin, reactive oxygen species, and circadian clocks. Antioxid. Redox Signal., 2014, 20(18), 2982-2996.
[http://dx.doi.org/10.1089/ars.2013.5645] [PMID: 24111846]
[4]
Ali, S.A.; Naaz, I.; Zaidi, K.U.; Ali, A.S. Recent updates in melanocyte function: The use of promising bioactive compounds for the treatment of hypopigmentary disorders. Mini Rev. Med. Chem., 2017, 17(9), 785-798.
[http://dx.doi.org/10.2174/1389557516666161223153953] [PMID: 28019642]
[5]
Zaidi, K.U.; Ali, S.A.; Ali, A.S. Natural melanogenesis stimulator a potential tool for the treatment of hypopigmentation disease. Intl. J. Mol. Biol., 2017, 2, 1-5.
[http://dx.doi.org/10.15406/ijmboa.2016.02.00012]
[6]
Zaidi, K.U.; Ali, S.A.; Ali, A.; Naaz, I. Natural tyrosinase inhibitors: Role of herbals in the treatment of hyperpigmentary disorders. Mini Rev. Med. Chem., 2019, 19(10), 796-808.
[http://dx.doi.org/10.2174/1389557519666190116101039] [PMID: 31244414]
[7]
Goding, C.R. Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev., 2000, 14(14), 1712-1728.
[PMID: 10898786]
[8]
Vance, K.W.; Goding, C.R. The transcription network regulating melanocyte development and melanoma. Pigment Cell Res., 2004, 17(4), 318-325.
[http://dx.doi.org/10.1111/j.1600-0749.2004.00164.x] [PMID: 15250933]
[9]
Sato, K.; Toriyama, M. Effect of Pyrroloquinoline Quinone (PQQ) on melanogenic protein expression in murine B16 melanoma. J. Dermatol. Sci., 2008, 8, 1-6.
[PMID: 19013771]
[10]
Jung, E.; Lee, J.; Huh, S.; Lee, J.; Kim, Y.S.; Kim, G.; Park, D. Phloridzin-induced melanogenesis is mediated by the cAMP signaling pathway. Food Chem. Toxicol., 2009, 47(10), 2436-2440.
[http://dx.doi.org/10.1016/j.fct.2009.06.039] [PMID: 19576939]
[11]
Lv, N.; Koo, J.H.; Yoon, H.Y.; Yu, J.; Kim, K.A.; Choi, I.W.; Kwon, K.B.; Kwon, K.S.; Kim, H.U.; Park, J.W.; Park, B.H. Effect of Angelica gigas extract on melanogenesis in B16 melanoma cells. Int. J. Mol. Med., 2007, 20(5), 763-767.
[PMID: 17912471]
[12]
Smalley, K.; Eisen, T. The involvement of p38 mitogen-activated protein kinase in the alpha-melanocyte stimulating hormone (alpha-MSH)-induced melanogenic and anti-proliferative effects in B16 murine melanoma cells. FEBS Lett., 2000, 476(3), 198-202.
[http://dx.doi.org/10.1016/S0014-5793(00)01726-9] [PMID: 10913613]
[13]
Lee, J.; Jung, E.; Park, J.; Jung, K.; Park, E.; Kim, J.; Hong, S.; Park, J.; Park, S.; Lee, S.; Park, D. Glycyrrhizin induces melanogenesis by elevating a cAMP level in b16 melanoma cells. J. Invest. Dermatol., 2005, 124(2), 405-411.
[http://dx.doi.org/10.1111/j.0022-202X.2004.23606.x] [PMID: 15675961]
[14]
Ebanks, J.P.; Wickett, R.R.; Boissy, R.E. Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration. Int. J. Mol. Sci., 2009, 10(9), 4066-4087.
[http://dx.doi.org/10.3390/ijms10094066] [PMID: 19865532]
[15]
Goreja, W.G. Black seed: natures miracle remedy; Amazing Herbs Press: New York, NY, 2013, p. 7.
[16]
Sharma, P.C.; Yelne, M.B.; Dennis, T.J. Database on medicinal plants used in Ayurveda. Central Council for Research in Ayurveda and Siddha, DEPTT of ISM & H Min of Health and Family Welfare; Government of India: New Delhi, 2005, pp. 420-440.
[17]
Negi, P.; Rathore, C.; Sharma, G. Thymoquinone (TQ) a potential therapeutic molecule: Role of colloidal carriers in its effective delivery. Recent Pat. Drug Deliv. Formul., 2018, 12(1), 3-22.
[http://dx.doi.org/10.2174/1872211311666171129121128] [PMID: 29189187]
[18]
Al-Ghamdi, M.S. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J. Ethnopharmacol., 2001, 76(1), 45-48.
[http://dx.doi.org/10.1016/S0378-8741(01)00216-1] [PMID: 11378280]
[19]
Ali, B.H.; Blunden, G. Pharmacological and toxicological properties of Nigella sativa. Phytother. Res., 2003, 17(4), 299-305.
[http://dx.doi.org/10.1002/ptr.1309] [PMID: 12722128]
[20]
Zaidi, K.U.; Ali, S.A.; Ali, A.S. Melanogenic effect of purified mushroom tyrosinase on B16F10 melanocytes: A phase contrast and immunofluorescence microscopic study. J Microsc Ultrastruct, 2017, 5(2), 82-89.
[http://dx.doi.org/10.1016/j.jmau.2016.07.002] [PMID: 30023240]
[21]
Kim, D.S.; Park, S.H.; Kwon, S.B.; Joo, Y.H.; Youn, S.W.; Sohn, U.D.; Park, K.C. Temperature regulates melanin synthesis in melanocytes. Arch. Pharm. Res., 2003, 26(10), 840-845.
[http://dx.doi.org/10.1007/BF02980030] [PMID: 14609133]
[22]
Sung, C.K.; Cho, S.H. The purification and characteristics of tyrosinase from ginger (Zingiber officinale rosc.). J. Biochem. Mol. Biol., 1992, 25, 564-572.
[23]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[PMID: 14907713]
[24]
Tsuboi, T.; Kondoh, H.; Hiratsuka, J.; Mishima, Y. Enhanced melanogenesis induced by tyrosinase gene-transfer increases boron-uptake and killing effect of boron neutron capture therapy for amelanotic melanoma. Pigment Cell Res., 1998, 11(5), 275-282.
[http://dx.doi.org/10.1111/j.1600-0749.1998.tb00736.x] [PMID: 9877098]
[25]
Zaidi, K.U.; Ali, S.A.; Ali, A.S. Effect of purified mushroom tyrosinase on melanin content and melanogenic protein expression. Biotechnol. Res. Int., 2016, 20169706214
[http://dx.doi.org/10.1155/2016/9706214] [PMID: 27699070]
[26]
Seo, G.Y.; Ha, Y.; Park, A.H.; Kwon, O.W.; Kim, Y.J. Leathesia difformis extract inhibits α-MSH-induced melanogenesis in B16F10 Cells via Down-Regulation of CREB signaling pathway. Int. J. Mol. Sci., 2019, 20(3), 536.
[http://dx.doi.org/10.3390/ijms20030536] [PMID: 30695994]
[27]
Ji, K.; Zhang, P.; Zhang, J.; Fan, R.; Liu, Y.; Yang, S.; Hu, S.; Liu, X.; Dong, C. MicroRNA 143-5p regulates alpaca melanocyte migration, proliferation and melanogenesis. Exp. Dermatol., 2018, 27(2), 166-171.
[http://dx.doi.org/10.1111/exd.13480] [PMID: 29230879]
[28]
Setty, S.R.; Opsin, A. Opsin3-A link to visible light-induced skin pigmentation. J. Invest. Dermatol., 2018, 138(1), 13-15.
[http://dx.doi.org/10.1016/j.jid.2017.09.025] [PMID: 29273144]
[29]
Takeyama, R.; Takekoshi, S.; Nagata, H.; Osamura, R.Y.; Kawana, S. Quercetin-induced melanogenesis in a reconstituted three-dimensional human epidermal model. J. Mol. Histol., 2004, 35(2), 157-165.
[http://dx.doi.org/10.1023/B:HIJO.0000023388.51625.6c] [PMID: 15328920]
[30]
Takekoshi, S.; Nagata, H.; Kitatani, K. Flavonoids enhance melanogenesis in human melanoma cells. Tokai J. Exp. Clin. Med., 2014, 39(3), 116-121.
[PMID: 25248426]
[31]
Sturm, R.A.; O’Sullivan, B.J.; Thomson, J.A.; Jamshidi, N.; Pedley, J.; Parsons, P.G. Expression studies of pigmentation and POU-domain genes in human melanoma cells. Pigment Cell Res., 1994, 7(4), 235-240.
[http://dx.doi.org/10.1111/j.1600-0749.1994.tb00055.x] [PMID: 7855069]
[32]
Lee, J.; Kim, Y.S.; Park, D. Rosmarinic acid induces melanogenesis through protein kinase A activation signaling. Biochem. Pharmacol., 2007, 74(7), 960-968.
[http://dx.doi.org/10.1016/j.bcp.2007.06.007] [PMID: 17651699]
[33]
Kim, D.S.; Cha, S.B.; Park, M.C.; Park, S.A.; Kim, H.S.; Woo, W.H.; Mun, Y.J. Scopoletin stimulates melanogenesis via cAMP/PKA pathway and partially p38 activation. Biol. Pharm. Bull., 2017, 40(12), 2068-2074.
[http://dx.doi.org/10.1248/bpb.b16-00690] [PMID: 28943528]
[34]
Moleephan, W.; Wittayalertpanyab, S.; Ruangrungsic, N. Effect of xanthoxylin on melanin content and melanogenic protein expression in B16F10 melanoma. Asian Biomed., 2012, 6, 413-422.
[35]
Zaidi, K.U.; Ali, S.A.; Ali, A.S. Purified mushroom tyrosinase induced melanogenic protein expression in B16F10 melanocytes: A Quantitative densitometric analysis. Open Med. Chem. J., 2018, 12, 36-47.
[http://dx.doi.org/10.2174/1874104501812010036] [PMID: 29541257]

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