DOI QR코드

DOI QR Code

Imatinib mesylate promotes melanogenesis through the modulation of p38 and MITF in murine cells

  • 투고 : 2024.07.23
  • 심사 : 2024.10.14
  • 발행 : 2025.01.15

초록

Imatinib mesylate is a targeted anti-cancer drug with skin pigmentation as a side effect. The action mechanism of imatinib mesylate on melanogenesis remains unclear. The purpose of this study was to elucidate the mechanism of imatinib mesylate on melanogenesis associated with the microphthalmia-associated transcription factor (MITF) signaling pathway in murine melanoma cells. This study revealed that imatinib mesylate increased tyrosinase activity but decreased hydrogen peroxide generation in B16F1 cells. Additionally, imatinib mesylate at 0.3-5 µM was nontoxic to the cells and promoted melanin production. Moreover, imatinib mesylate at 5 µM increased the expression levels of TRP-2 and p38 related to melanogenesis compared with the blank group in western blot and immunofluorescence staining analyses. The expression level of p-MITF in the nucleus was increased in the presence of imatinib mesylate compared with the blank group. These results suggest that imatinib mesylate could promote melanogenesis through the modulation of p38 and MITF.

키워드

과제정보

We appreciate Ms. SoJeong Jeon for her valuable suggestions and excellent analytical assistance.

참고문헌

  1. Baudino AT (2015) Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol 12:3–20. https://doi.org/10.2174/1570163812666150602144310
  2. Albayrak M, Celebi H, Albayrak A et al (2011) Serious skin reaction associated with imatinib in a patient with chronic myeloid leukemia. Eurasian J Med 43:192–195. https://doi.org/10.5152/EAJM.2011.42
  3. Alexandrescu DT, Dasanu CA, Farzanmehr H, Kauffman CL (2008) Persistent cutaneous hyperpigmentation after tyrosine kinase inhibition with imatinib for GIST. Dermatol Online J 14. https://doi.org/10.5070/D3472203P2
  4. Aoki H, Motohashi T, Yoshimura N et al (2005) Cooperative and indispensable roles of endothelin 3 and KIT signalings in melanocyte development. Dev Dyn 233:407–417. https://doi.org/10.1002/DVDY.20340
  5. Boo YC (2021) Arbutin as a skin depigmenting agent with antimelanogenic and antioxidant properties. Antioxidants 10:1–22. https://doi.org/10.3390/ANTIOX10071129
  6. Chau WK, Ip CK, Mak ASC et al (2012) c-KIT mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/β-catenin–ATP-binding cassette G2 signaling. Oncogene 32:2767–2781. https://doi.org/10.1038/onc.2012.290
  7. D'Mello SAN, Finlay GJ, Baguley BC, Askarian-Amiri ME (2016) Signaling pathways in melanogenesis. Int J Mol Sci 17:1144. https://doi.org/10.3390/IJMS17071144
  8. Di Tullio F, Mandel VD, Scotti R et al (2018) Imatinib-induced diffuse hyperpigmentation of the oral mucosa, the skin, and the nails in a patient affected by chronic myeloid leukemia: report of a case and review of the literature. Int J Dermatol 57:784–790. https://doi.org/10.1111/IJD.13931
  9. Farris PK (2018) Topical skin care and the cosmetic patient. J Cosmet Dermatol 18:798–805. https://doi.org/10.1016/B978-0-323-35876-7.00005-4
  10. Fraunfelder FW, Solomon J, Druker BJ et al (2004) Ocular sideeffects associated with imatinib mesylate (Gleevec®). J Ocul Pharmacol Ther 19:371–375. https://doi.org/10.1089/108076803322279426
  11. Gómez Fernández C, Sendagorta Cudós E, Casado Verrier B et al (2010) Oral lichenoid eruption associated with imatinib treatment. Eur J Dermatology 20:127–128. https://doi.org/10.1684/EJD.2010.0818
  12. Gutknecht M, Geiger J, Joas S et al (2015) The transcription factor MITF is a critical regulator of GPNMB expression in dendritic cells. Cell Commun Signal 13:1–15. https://doi.org/10.1186/S12964-015-0099-5
  13. Hasan SP, Dinh K, Lombardo F et al (2003) Hypopigmentation in an African patient treated with imatinib mesylate: a case report. J Natl Med Assoc 95:722
  14. Jian D, Jiang D, Su J et al (2011) Diethylstilbestrol enhances melanogenesis via cAMP-PKA-mediating up-regulation of tyrosinase and MITF in mouse B16 melanoma cells. Steroids 76:1297–1304. https://doi.org/10.1016/J.STEROIDS.2011.06.008
  15. Kang SH, Kim MM (2021) Spermidine promotes melanin production through an MITF signalling pathway. Cell Biochem Funct 39:536–545. https://doi.org/10.1002/CBF.3619
  16. Kim SS, Kim MJ, Choi YH et al (2013) Down-regulation of tyrosinase, TRP-1, TRP-2 and MITF expressions by citrus presscakes in murine B16 F10 melanoma. Asian Pac J Trop Biomed 3:617–622. https://doi.org/10.1016/S2221-1691(13)60125-2
  17. Lee E, Kim M-M (2019) Effect of ethanolic extracts mixed with grains and fallopia multiflora on melanogenesis. J Life Sci 29:461–469. https://doi.org/10.5352/JLS.2019.29.4.461
  18. Levy C, Khaled M, Fisher DE (2006) MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12:406–414. https://doi.org/10.1016/J.MOLMED.2006.07.008
  19. Maranduca MA, Branisteanu D, Serban DN et al (2019) Synthesis and physiological implications of melanic pigments. Oncol Lett 17:4183–4187. https://doi.org/10.3892/OL.2019.10071
  20. Mattsson U, Halbritter S, Mörner Serikoff E et al (2011) Oral pigmentation in the hard palate associated with imatinib mesylate therapy: a report of three cases. Oral Surg, Oral Med Oral Pathol Oral Radiol Endodontol 111:e12–e16. https://doi.org/10.1016/J.TRIPLEO.2010.11.006
  21. Mcpherson T, Sherman V, Turner R (2009) Imatinib-associated hyperpigmentation, a side effect that should be recognized. J Eur Acad Dermatology Venereol 23:82–83. https://doi.org/10.1111/J.1468-3083.2008.02706.X
  22. Oliveira SR, de Azevedo Branco LG, Rocha AL et al (2019) Association of oral mucosa hyperpigmentation with imatinib mesylate use: a cross-sectional study and a systematic literature review. Clin Oral Investig 23:4371–4382. https://doi.org/10.1007/S00784-019-02886-0/METRICS
  23. Pillaiyar T, Manickam M, Namasivayam V (2017) Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors. J Enzyme Inhib Med Chem 32:403–425. https://doi.org/10.1080/14756366.2016.1256882
  24. Piris-Villaespesa M, Alvarez-Twose I (2020) Systemic mastocytosis: following the tyrosine kinase inhibition roadmap. Front Pharmacol 11:1–8. https://doi.org/10.3389/FPHAR.2020.00443/BIBTEX
  25. Pretel-Irazabal M, Tuneu-Valls A, Ormaechea-Pérez N (2014) Adverse skin effects of imatinib, a tyrosine kinase inhibitor. Actas Dermosifiliogr 105:655–662. https://doi.org/10.1016/J.ADENGL.2014.07.010
  26. Sacha T (2014) Imatinib in chronic myeloid leukemia: an overview. Mediterr J Hematol Infect Dis 6:1–9. https://doi.org/10.4084/MJHID.2014.007
  27. Scheinfeld N (2006) Imatinib mesylate and dermatology part 2: a review of the cutaneous side effects of imatinib mesylate. J Drugs Dermatol 5:228–231
  28. Siegrist W, Eberle AN (1986) In situ melanin assay for MSH using mouse B16 melanoma cells in culture. Anal Biochem 159:191–197. https://doi.org/10.1016/0003-2697(86)90327-1
  29. Singh M, Mukhopadhyay K (2014) Alpha-melanocyte stimulating hormone: an emerging anti-inflammatory antimicrobial peptide. Biomed Res Int 2014:874610. https://doi.org/10.1155/2014/874610
  30. Singh N, Bakhshi S (2007) Imatinib-induced dental hyperpigmentation in childhood chronic myeloid leukemia. J Pediatr Hematol Oncol 29:208–209. https://doi.org/10.1097/MPH.0B013E318033A76C
  31. Steele JC, Triantafyllou A, Rajlawat BP, Field EA (2012) Oral mucosal hyperpigmentation and horizontal melanonychia caused by imatinib. Clin Exp Dermatol 37:432–433. https://doi.org/10.1111/J.1365-2230.2011.04196.X
  32. Tsao AS, Kantarjian H, Cortes J et al (2003) Imatinib mesylate causes hypopigmentation in the skin. Cancer 98:2483–2487. https://doi.org/10.1002/CNCR.11812
  33. Zhao Y, Liu L, Wang Y et al (2009) Efficacy and prognosis of chronic myeloid leukemia treated with imatinib mesylate in a Chinese population. Int J Hematol 89:445–451. https://doi.org/10.1007/S12185-009-0292-7
  34. Zugazagoitia J, Guedes C, Ponce S et al (2016) Current challenges in cancer treatment. Clin Ther 38:1551–1566. https://doi.org/10.1016/J.CLINTHERA.2016.03.026
  35. Zuo K, Kuang D, Wang Y et al (2016) SCF/c-KIT transactivates CXCR4-serine 339 phosphorylation through G protein-coupled receptor kinase 6 and regulates cardiac stem cell migration. Sci Rep 6:1–12. https://doi.org/10.1038/srep26812