Skip to main content
Erschienen in: Journal of Natural Medicines 1/2019

Open Access 01.01.2019 | Original Paper

Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin and c-Raf–MEK1–ERK signaling axis

verfasst von: Toshio Kaneda, Misaki Matsumoto, Yayoi Sotozono, Satoshi Fukami, Alfarius Eko Nugroho, Yusuke Hirasawa, Hadi A. Hamid A, Hiroshi Morita

Erschienen in: Journal of Natural Medicines | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

We recently reported that (23R, 24E)-23-acetoxymangiferonic acid (23R-AMA), a cycloartane triterpenoid isolated by activity-guided separation from a methanol extract of Garcinia sp. bark, inhibited melanin production via inhibition of tyrosinase (TYR) expression in the B16-F10 melanoma cell line. Since 23R-AMA also inhibited microphthalmia-associated transcription factor (MITF) expression, an upstream factor of TYR, these features of 23R-AMA were thought to be appropriate for development of whitening cosmetics. However, 23R-AMA exhibited growth inhibition other than inhibition of melanin production in B16-F10 cells. Therefore, we investigated biological activities of 23R-AMA in detail, focused on its application as an anti-melanoma compound. In this study, we demonstrated that 23R-AMA inhibited cell proliferation and basic FGF (bFGF)-induced migration in B16-F10 cells. Furthermore, 23R-AMA promoted ser45/thr41 phosphorylation of β-catenin and suppressed its intranuclear accumulation, which was suggested to be related to inhibition of MITF expression. The transcriptional activity of MITF is known to be regulated by phosphorylation via activated ERK. Further investigation revealed that 23R-AMA inhibited phosphorylation of c-Raf, MEK-1, and ERK, and also that of upstream molecules including FAK and c-Src. These results suggested that 23R-AMA inhibited growth and migration of B16-F10 melanoma by regulating both MITF expression and its activity. The activities of 23R-AMA reported in this study are new aspects of cycloartane triterpenoids.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat D’Mello SAN, Finlay GJ, Baguley BC, Askarian-Amiri ME (2016) Signaling pathways in melanogenesis. Int J Mol Sci 17:1144CrossRef D’Mello SAN, Finlay GJ, Baguley BC, Askarian-Amiri ME (2016) Signaling pathways in melanogenesis. Int J Mol Sci 17:1144CrossRef
2.
Zurück zum Zitat Matthews NH, Li W-Q, Qureshi AA, Weinstock MA, Cho E (2017) Epidemiology of melanoma. In: Ward WH, Farma JM (eds) Cutaneous melanoma: etiology and therapy. Codon, Brisbane Matthews NH, Li W-Q, Qureshi AA, Weinstock MA, Cho E (2017) Epidemiology of melanoma. In: Ward WH, Farma JM (eds) Cutaneous melanoma: etiology and therapy. Codon, Brisbane
3.
Zurück zum Zitat Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR (2005) Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436:117CrossRef Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR (2005) Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436:117CrossRef
4.
Zurück zum Zitat Vachtenheim J, Novotna H (1999) Expression of genes for microphthalmia isoforms, Pax3 and MSG1, in human melanomas. Cell Mol Biol 45:1075–1082PubMed Vachtenheim J, Novotna H (1999) Expression of genes for microphthalmia isoforms, Pax3 and MSG1, in human melanomas. Cell Mol Biol 45:1075–1082PubMed
5.
Zurück zum Zitat Larribere L, Hilmi C, Khaled M, Gaggioli C, Bille K, Auberger P, Ortonne JP, Ballotti R, Bertolotto C (2005) The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis. Genes Dev 19:1980–1985CrossRef Larribere L, Hilmi C, Khaled M, Gaggioli C, Bille K, Auberger P, Ortonne JP, Ballotti R, Bertolotto C (2005) The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis. Genes Dev 19:1980–1985CrossRef
6.
Zurück zum Zitat Nugroho AE, Matsumoto M, Sotozono Y, Kaneda T, Hadi AHA, Morita H (2018) Cycloartane triterpenoids with anti-melanin deposition activity. Nat Prod Commun 13(7):809–812 Nugroho AE, Matsumoto M, Sotozono Y, Kaneda T, Hadi AHA, Morita H (2018) Cycloartane triterpenoids with anti-melanin deposition activity. Nat Prod Commun 13(7):809–812
7.
Zurück zum Zitat Anjaneyulu V, Satyanarayana P, Viswanadham KN, Jyothi VG, Rao KN, Radhika P (1999) Triterpenoids from Mangifera indica. Phytochemistry 50:1229–1236CrossRef Anjaneyulu V, Satyanarayana P, Viswanadham KN, Jyothi VG, Rao KN, Radhika P (1999) Triterpenoids from Mangifera indica. Phytochemistry 50:1229–1236CrossRef
8.
Zurück zum Zitat Sakagami Y, Iinuma M, Piyasena KG, Dharmaratne HR (2005) Antibacterial activity of alpha-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics. Phytomedicine 12:203–208CrossRef Sakagami Y, Iinuma M, Piyasena KG, Dharmaratne HR (2005) Antibacterial activity of alpha-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics. Phytomedicine 12:203–208CrossRef
9.
Zurück zum Zitat Jena BS, Jayaprakasha GK, Singh RP, Sakariah KK (2002) Chemistry and biochemistry of (−)-hydroxycitric acid from Garcinia. J Agric Food Chem 50:10–22CrossRef Jena BS, Jayaprakasha GK, Singh RP, Sakariah KK (2002) Chemistry and biochemistry of (−)-hydroxycitric acid from Garcinia. J Agric Food Chem 50:10–22CrossRef
10.
Zurück zum Zitat Zhang H-Z, Kasibhatla S, Wang Y, Herich J, Guastella J, Tseng B, Drewe J, Cai SX (2004) Discovery, characterization and SAR of gambogic acid as a potent apoptosis inducer by a HTS assay. Bioorg Med Chem 12:309–317CrossRef Zhang H-Z, Kasibhatla S, Wang Y, Herich J, Guastella J, Tseng B, Drewe J, Cai SX (2004) Discovery, characterization and SAR of gambogic acid as a potent apoptosis inducer by a HTS assay. Bioorg Med Chem 12:309–317CrossRef
11.
Zurück zum Zitat Toume K, Nakazawa T, Hoque T, Ohtsuki T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M (2012) Cycloartane triterpenes and ingol diterpenes isolated from Euphorbia neriifolia in a screening program for death-receptor expression-enhancing activity. Planta Med 78:1370–1377CrossRef Toume K, Nakazawa T, Hoque T, Ohtsuki T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M (2012) Cycloartane triterpenes and ingol diterpenes isolated from Euphorbia neriifolia in a screening program for death-receptor expression-enhancing activity. Planta Med 78:1370–1377CrossRef
12.
Zurück zum Zitat Toume K, Nakazawa T, Ohtsuki T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M (2011) Cycloartane triterpenes isolated from Combretum quadrangulare in a screening program for death-receptor expression enhancing activity. J Nat Prod 74:249–255CrossRef Toume K, Nakazawa T, Ohtsuki T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M (2011) Cycloartane triterpenes isolated from Combretum quadrangulare in a screening program for death-receptor expression enhancing activity. J Nat Prod 74:249–255CrossRef
13.
Zurück zum Zitat Khan MTH, Khan SB, Ather A (2006) Tyrosinase inhibitory cycloartane type triterpenoids from the methanol extract of the whole plant of Amberboa ramosa Jafri and their structure-activity relationship. Bioorg Med Chem 14:938–943CrossRef Khan MTH, Khan SB, Ather A (2006) Tyrosinase inhibitory cycloartane type triterpenoids from the methanol extract of the whole plant of Amberboa ramosa Jafri and their structure-activity relationship. Bioorg Med Chem 14:938–943CrossRef
14.
Zurück zum Zitat Schreiber E, Matthias P, Müller MM, Schaffner W (1989) Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nucleic Acids Res 17:6419CrossRef Schreiber E, Matthias P, Müller MM, Schaffner W (1989) Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nucleic Acids Res 17:6419CrossRef
15.
Zurück zum Zitat Tachibana M (2000) MITF: a stream flowing for pigment cells. Pigment Cell Res 13:230–240CrossRef Tachibana M (2000) MITF: a stream flowing for pigment cells. Pigment Cell Res 13:230–240CrossRef
16.
Zurück zum Zitat Maher MT, Mo R, Flozak AS, Peled ON, Gottardi CJ (2010) β-Catenin phosphorylated at serine 45 is spatially uncoupled from β-catenin phosphorylated in the GSK3 domain: implications for signaling. PLoS One 5:e10184CrossRef Maher MT, Mo R, Flozak AS, Peled ON, Gottardi CJ (2010) β-Catenin phosphorylated at serine 45 is spatially uncoupled from β-catenin phosphorylated in the GSK3 domain: implications for signaling. PLoS One 5:e10184CrossRef
17.
Zurück zum Zitat McGill GG, Haq R, Nishimura EK, Fisher DE (2006) c-Met expression is regulated by mitf in the melanocyte lineage. J Biol Chem 281:10365–10373CrossRef McGill GG, Haq R, Nishimura EK, Fisher DE (2006) c-Met expression is regulated by mitf in the melanocyte lineage. J Biol Chem 281:10365–10373CrossRef
18.
Zurück zum Zitat Wu M, Hemesath TJ, Takemoto CM, Horstmann MA, Wells AG, Price ER, Fisher DZ, Fisher DE (2000) c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev 14:301–312PubMedPubMedCentral Wu M, Hemesath TJ, Takemoto CM, Horstmann MA, Wells AG, Price ER, Fisher DZ, Fisher DE (2000) c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev 14:301–312PubMedPubMedCentral
19.
Zurück zum Zitat Gear H, Williams H, Kemp EG, Roberts F (2004) BRAF mutations in conjunctival melanoma. Invest Ophthalmol Vis Sci 45:2484–2488CrossRef Gear H, Williams H, Kemp EG, Roberts F (2004) BRAF mutations in conjunctival melanoma. Invest Ophthalmol Vis Sci 45:2484–2488CrossRef
20.
Zurück zum Zitat Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JWC, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417:949CrossRef Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JWC, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417:949CrossRef
21.
Zurück zum Zitat Kolch W (2000) Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J 351:289–305CrossRef Kolch W (2000) Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J 351:289–305CrossRef
22.
Zurück zum Zitat Frame MC (2004) Newest findings on the oldest oncogene; how activated src does it. J Cell Sci 117:989–998CrossRef Frame MC (2004) Newest findings on the oldest oncogene; how activated src does it. J Cell Sci 117:989–998CrossRef
23.
Zurück zum Zitat Bosnjak M, Dolinsek T, Cemazar M, Kranjc S, Blagus T, Markelc B, Stimac M, Zavrsnik J, Kamensek U, Heller L, Bouquet C, Turk B, Sersa G (2015) Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma. Gene Ther 22:578CrossRef Bosnjak M, Dolinsek T, Cemazar M, Kranjc S, Blagus T, Markelc B, Stimac M, Zavrsnik J, Kamensek U, Heller L, Bouquet C, Turk B, Sersa G (2015) Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma. Gene Ther 22:578CrossRef
24.
Zurück zum Zitat Qian F, Vaux DL, Weissman IL (1994) Expression of the integrin α4β1 on melanoma cells can inhibit the invasive stage of metastasis formation. Cell 77:335–347CrossRef Qian F, Vaux DL, Weissman IL (1994) Expression of the integrin α4β1 on melanoma cells can inhibit the invasive stage of metastasis formation. Cell 77:335–347CrossRef
25.
Zurück zum Zitat Wang D, Ma Z (2009) Cytotoxic activity of cycloartane triterpenoids from Sphaerophysa salsula. Nat Prod Commun 4:23–25PubMed Wang D, Ma Z (2009) Cytotoxic activity of cycloartane triterpenoids from Sphaerophysa salsula. Nat Prod Commun 4:23–25PubMed
26.
Zurück zum Zitat Li F, Awale S, Zhang H, Tezuka Y, Esumi H, Kadota S (2009) Chemical constituents of propolis from Myanmar and their preferential cytotoxicity against a human pancreatic cancer cell line. J Nat Prod 72:1283–1287CrossRef Li F, Awale S, Zhang H, Tezuka Y, Esumi H, Kadota S (2009) Chemical constituents of propolis from Myanmar and their preferential cytotoxicity against a human pancreatic cancer cell line. J Nat Prod 72:1283–1287CrossRef
27.
Zurück zum Zitat Tian Z, Si J, Chang Q, Zhou L, Chen S, Xiao P, Wu E (2007) Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma. BMC Cancer 7:237–237CrossRef Tian Z, Si J, Chang Q, Zhou L, Chen S, Xiao P, Wu E (2007) Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma. BMC Cancer 7:237–237CrossRef
28.
Zurück zum Zitat McGill GG, Horstmann M, Widlund HR, Du J, Motyckova G, Nishimura EK, Lin Y-L, Ramaswamy S, Avery W, Ding H-F, Jordan SA, Jackson IJ, Korsmeyer SJ, Golub TR, Fisher DE (2002) Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 109:707–718CrossRef McGill GG, Horstmann M, Widlund HR, Du J, Motyckova G, Nishimura EK, Lin Y-L, Ramaswamy S, Avery W, Ding H-F, Jordan SA, Jackson IJ, Korsmeyer SJ, Golub TR, Fisher DE (2002) Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 109:707–718CrossRef
29.
Zurück zum Zitat Du J, Widlund HR, Horstmann MA, Ramaswamy S, Ross K, Huber WE, Nishimura EK, Golub TR, Fisher DE (2004) Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF. Cancer Cell 6:565–576CrossRef Du J, Widlund HR, Horstmann MA, Ramaswamy S, Ross K, Huber WE, Nishimura EK, Golub TR, Fisher DE (2004) Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF. Cancer Cell 6:565–576CrossRef
30.
Zurück zum Zitat Marais R, Light Y, Paterson HF, Marshall CJ (1995) Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation. EMBO J 14:3136–3145CrossRef Marais R, Light Y, Paterson HF, Marshall CJ (1995) Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation. EMBO J 14:3136–3145CrossRef
31.
Zurück zum Zitat Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee M-K, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS (2010) Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468:973CrossRef Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee M-K, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS (2010) Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468:973CrossRef
32.
Zurück zum Zitat Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, Dias-Santagata D, Stubbs H, Lee DY, Singh A, Drew L, Haber DA, Settleman J (2008) Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res 68:4853–4861CrossRef Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, Dias-Santagata D, Stubbs H, Lee DY, Singh A, Drew L, Haber DA, Settleman J (2008) Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res 68:4853–4861CrossRef
33.
Zurück zum Zitat Schlaepfer DD, Hauck CR, Sieg DJ (1999) Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71:435–478CrossRef Schlaepfer DD, Hauck CR, Sieg DJ (1999) Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71:435–478CrossRef
34.
Zurück zum Zitat Kuphal S, Bauer R, Bosserhoff A-K (2005) Integrin signaling in malignant melanoma. Cancer Metastasis Rev 24:195–222CrossRef Kuphal S, Bauer R, Bosserhoff A-K (2005) Integrin signaling in malignant melanoma. Cancer Metastasis Rev 24:195–222CrossRef
35.
Zurück zum Zitat Aznavoorian S, Stracke ML, Parsons J, McClanahan J, Liotta LA (1996) Integrin αvβ3 mediates chemotactic and haptotactic motility in human melanoma cells through different signaling pathways. J Biol Chem 271:3247–3254CrossRef Aznavoorian S, Stracke ML, Parsons J, McClanahan J, Liotta LA (1996) Integrin αvβ3 mediates chemotactic and haptotactic motility in human melanoma cells through different signaling pathways. J Biol Chem 271:3247–3254CrossRef
36.
Zurück zum Zitat Frame MC (2002) Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta 1602:114–130PubMed Frame MC (2002) Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta 1602:114–130PubMed
37.
Zurück zum Zitat Ferguson J, Arozarena I, Ehrhardt M, Wellbrock C (2013) Combination of MEK and SRC inhibition suppresses melanoma cell growth and invasion. Oncogene 32:86–96CrossRef Ferguson J, Arozarena I, Ehrhardt M, Wellbrock C (2013) Combination of MEK and SRC inhibition suppresses melanoma cell growth and invasion. Oncogene 32:86–96CrossRef
Metadaten
Titel
Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin and c-Raf–MEK1–ERK signaling axis
verfasst von
Toshio Kaneda
Misaki Matsumoto
Yayoi Sotozono
Satoshi Fukami
Alfarius Eko Nugroho
Yusuke Hirasawa
Hadi A. Hamid A
Hiroshi Morita
Publikationsdatum
01.01.2019
Verlag
Springer Singapore
Erschienen in
Journal of Natural Medicines / Ausgabe 1/2019
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-018-1233-7

Weitere Artikel der Ausgabe 1/2019

Journal of Natural Medicines 1/2019 Zur Ausgabe