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Open AccessArticle

Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition

1
Biobank and Tissue Bank, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
2
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, 70 Lien-Hai Road, Kaohsiung 80424, Taiwan
3
Doctoral Degree Program in Marine Biotechnology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
4
Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
5
Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
6
Department of Dermatology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 81362, Taiwan
7
Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 681; https://doi.org/10.3390/ijms21020681
Received: 13 November 2019 / Revised: 16 January 2020 / Accepted: 17 January 2020 / Published: 20 January 2020
(This article belongs to the Special Issue Signaling in Melanoma)
Melanotan II (MTII), a synthetic analogue of the alpha-melanocyte stimulating hormone (α-MSH), has been applied for skin tanning in humans. However, the carcinogenic consequence of topical MTII has been equivocal. This study aims to delineate the anti-neoplastic efficacy and mechanism of MTII using the B16-F10 melanoma model in vitro and in vivo. It was found that, despite a lack of influence on proliferation, MTII potently inhibited the migration, invasion, and colony-forming capability of melanoma cells. Moreover, topical MTII application significantly attenuated the tumor progression in mice bearing established melanoma. Histological analysis revealed that MTII therapy induced apoptosis while inhibiting the proliferation and neovaluarization in melanoma tissues. By immunoblot and immunohistochemical analysis, it was found that MTII dose-dependently increased the phosphatase and tensin homolog (PTEN) protein level while reducing PTEN phosphorylation, which resulted in the inhibition of AKT/nuclear factor kappa B (NFκB) signaling. Consistently, MTII treatment inhibited cyclooxygenase II (COX-2) expression and prostaglandin E2 (PGE2) production in melanoma cells. Finally, studies of antibody neutralization suggest that the melanocortin 1 receptor (MC1R) plays a critical role in MTII-induced PTEN upregulation and melanoma suppression. Together, these results indicate that MTII elicits PTEN upregulation via MC1R, thereby suppressing melanoma progression through downregulating COX-2/PGE2 signaling. Hence, topical MTII therapy may facilitate a novel therapeutic strategy against melanoma. View Full-Text
Keywords: MTII; Melanoma; PTEN; COX-2; PGE2 MTII; Melanoma; PTEN; COX-2; PGE2
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MDPI and ACS Style

Wu, J.-C.; Tsai, H.-E.; Hsiao, Y.-H.; Wu, J.-S.; Wu, C.-S.; Tai, M.-H. Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition. Int. J. Mol. Sci. 2020, 21, 681. https://doi.org/10.3390/ijms21020681

AMA Style

Wu J-C, Tsai H-E, Hsiao Y-H, Wu J-S, Wu C-S, Tai M-H. Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition. International Journal of Molecular Sciences. 2020; 21(2):681. https://doi.org/10.3390/ijms21020681

Chicago/Turabian Style

Wu, Jian-Ching; Tsai, Han-En; Hsiao, Yi-Hsiang; Wu, Ji-Syuan; Wu, Chieh-Shan; Tai, Ming-Hong. 2020. "Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition" Int. J. Mol. Sci. 21, no. 2: 681. https://doi.org/10.3390/ijms21020681

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