Guggulsterone inhibits melanogenesis in B16 murine melanoma cells by downregulating tyrosinase expression

Koo,Jeung-Hyun; Rhee,Kyoung-Suk; Koh,Hyoung-Won; Jang,Hyun-Young; Park,Byung-Hyun; Park,Jin-Woo

doi:10.3892/ijmm.2012.1057

Guggulsterone inhibits melanogenesis in B16 murine melanoma cells by downregulating tyrosinase expression

Authors:
- Jeung-Hyun Koo
- Kyoung-Suk Rhee
- Hyoung-Won Koh
- Hyun-Young Jang
- Byung-Hyun Park
- Jin-Woo Park
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Affiliations: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea
Published online on: July 12, 2012 https://doi.org/10.3892/ijmm.2012.1057
Pages: 974-978

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Abstract

In the present study, we investigated the effect of guggulsterone on melanogenesis in B16 melanoma cells and elucidated its possible mechanism of action. The effects of guggulsterone on melanogenesis were determined by assaying melanin synthesis and cellular tyrosinase activity in B16/F10 mouse melanoma cells. Guggulsterone dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis and cellular tyrosinase activity with no cytotoxicity. Decreased melanin biosynthesis was accompanied by the reduced expression of melanogenesis-related genes, such as tyrosinase, microphthalmia-associated transcription factor, tyrosinase-related protein (TRP)-1 and TRP-2. Guggulsterone also inhibited α-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. Co-incubation with chenodeoxycholic acid, a well-known farnesoid-X receptor agonist, did not affect IBMX-induced melanogenesis. These results suggest that guggulsterone exerts a melanogenic inhibitory effect through the downregulation of tyrosinase expression.

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1.	Y YamaguchiVJ HearingPhysiological factors that regulate skin pigmentationBiofactors35193199200910.1002/biof.2919449448
2.	VJ HearingM JimenezMammalian tyrosinase - the critical regulatory control point in melanocyte pigmentationInt J Biochem1911411147198710.1016/0020-711X(87)90095-43125075
3.	K YokoyamaK YasumotoH SuzukiS ShibaharaCloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expressionJ Biol Chem26927080270871994
4.	T KobayashiK UrabeA WinderTyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesisEMBO J135818582519947813420
5.	GE CostinVJ HearingHuman skin pigmentation: melanocytes modulate skin color in response to stressFASEB J21976994200710.1096/fj.06-6649rev17242160
6.	R BuscaR BallottiCyclic AMP a key messenger in the regulation of skin pigmentationPigment Cell Res136069200010.1034/j.1600-0749.2000.130203.x10841026
7.	S ImO MoroF PengActivation of the cyclic AMP pathway by alpha-melanotropin mediates the response of human melanocytes to ultraviolet B radiationCancer Res58475419989426056
8.	C BertolottoP AbbeTJ HemesathMicrophthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytesJ Cell Biol142827835199810.1083/jcb.142.3.8279700169
9.	P WanY HuL HeRegulation of melanocyte pivotal transcription factor MITF by some other transcription factorsMol Cell Biochem354241246201110.1007/s11010-011-0823-421519923
10.	CJ SinalFJ GonzalezGuggulsterone: an old approach to a new problemTrends Endocrinol Metab13275276200210.1016/S1043-2760(02)00640-912163224
11.	NL UrizarDD MooreGUGULIPID: a natural cholesterol-lowering agentAnnu Rev Nutr23303313200310.1146/annurev.nutr.23.011702.07310212626688
12.	NL UrizarAB LivermanDT DoddsA natural product that lowers cholesterol as an antagonist ligand for FXRScience29617031706200210.1126/science.107289111988537
13.	J WuC XiaJ MeierS LiX HuDS LalaThe hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMol Endocrinol1615901597200210.1210/mend.16.7.089412089353
14.	J CuiL HuangA ZhaoGuggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpJ Biol Chem2781021410220200310.1074/jbc.M20932320012525500
15.	KR StayrookKS BramlettRS SavkurRegulation of carbohydrate metabolism by the farnesoid X receptorEndocrinology146984991200510.1210/en.2004-096515564327
16.	N LvMY SongEK KimJW ParkKB KwonBH ParkGuggulsterone, a plant sterol, inhibits NF-κB activation and protects pancreatic beta cells from cytokine toxicityMol Cell Endocrinol28949592008
17.	YR LeeJH LeeEM NohGuggulsterone blocks IL-1β-mediated inflammatory responses by suppressing NF-κB activation in fibroblast-like synoviocytesLife Sci82120312092008
18.	JH KooI LeeSK YunHU KimBH ParkJW ParkSaponified evening primrose oil reduces melanogenesis in B16 melanoma cells and reduces UV-induced skin pigmentation in humansLipids45401407201010.1007/s11745-010-3405-420352496
19.	MS EllerBA GilchrestTanning as part of the eukaryotic SOS responsePigment Cell Res13Suppl 8S94S97200010.1034/j.1600-0749.13.s8.17.x11041364
20.	JA BeavoNL RogersOB CroffordJG HardmanEW SutherlandEV NewmanEffects of xanthine derivatives on lipolysis and on adenosine 3′,5′-monophosphate phosphodiesterase activityMol Pharmacol65976031970
21.	K WakamatsuA GrahamD CookAJ ThodyCharacterisation of ACTH peptides in human skin and their activation of the melanocortin-1 receptorPigment Cell Res10288297199710.1111/j.1600-0749.1997.tb00688.x9359624
22.	T TamagawaH NikiA NikiInsulin release independent of a rise in cytosolic free Ca²⁺ by forskolin and phorbol esterFEBS Lett183430432198510.1016/0014-5793(85)80825-52985438
23.	HY ParkV RussakovskyS OhnoBA GilchrestThe beta isoform of protein kinase C stimulates human melanogenesis by activating tyrosinase in pigment cellsJ Biol Chem268117421174919937685020
24.	M SasakiT HorikoshiH UchiwaY MiyachiUp-regulation of tyrosinase gene by nitric oxide in human melanocytesPigment Cell Res13248252200010.1034/j.1600-0749.2000.130406.x10952392
25.	DS KimSH ParkSB KwonK LiSW YounKC Park(-)-Epigallocatechin-3-gallate and hinokitiol reduce melanin synthesis via decreased MITF productionArch Pharm Res27334339200410.1007/BF0298006915089040
26.	JH KooHT KimHY YoonEffect of xanthohumol on melanogenesis in B16 melanoma cellsExp Mol Med40313319200810.3858/emm.2008.40.3.31318587269
27.	N LvJH KooHY YoonEffect of Angelica gigas extract on melanogenesis in B16 melanoma cellsInt J Mol Med207637672007
28.	B SharmaR SalunkeS SrivastavaC MajumderP RoyEffects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic ratsFood Chem Toxicol4726312639200919635521
29.	S SarfarazIA SiddiquiDN SyedF AfaqH MukhtarGuggulsterone modulates MAPK and NF-κB pathways and inhibits skin tumorigenesis in SENCAR miceCarcinogenesis2920112018200818684729