UP256 Inhibits Hyperpigmentation by Tyrosinase Expression/Dendrite Formation via Rho-Dependent Signaling and by Primary Cilium Formation in Melanocytes
Skin hyperpigmentation is generally characterized by increased synthesis and deposition of melanin in the skin. UP256, containing bakuchiol, is a well-known medication for acne vulgaris. Acne sometimes leaves dark spots on the skin, and we hypothesized that UP256 may be effective against hyperpigmen...
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doaj-923fe99365114da9b32a26c73e201e632020-11-25T01:19:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-01215341534110.3390/ijms21155341UP256 Inhibits Hyperpigmentation by Tyrosinase Expression/Dendrite Formation via Rho-Dependent Signaling and by Primary Cilium Formation in Melanocytes Min Cheol Kang0Jae-Wook Lee1Taek Hwan Lee2Lalita Subedi3Hussain M. Wahedi4Seon-Gil Do5Eunju Shin6Eun-Yi Moon7Sun Yeou Kim8College of Pharmacy, Gachon University 191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaDepartment of Bioscience and Biotechnology, Sejong University, Seoul 05006, KoreaCollege of Pharmacy, Yonsei University, Songdo-dong, Yeonsu-gu, Incheon 21936, KoreaCollege of Pharmacy, Gachon University 191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaDepartment of Biological Sciences, National University of Medical Sciences, Mall Road, Rawalpindi 46000, PakistanWellness R&D Center, Univera, Inc., Seoul 04782, KoreaWellness R&D Center, Univera, Inc., Seoul 04782, KoreaDepartment of Bioscience and Biotechnology, Sejong University, Seoul 05006, KoreaCollege of Pharmacy, Gachon University 191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaSkin hyperpigmentation is generally characterized by increased synthesis and deposition of melanin in the skin. UP256, containing bakuchiol, is a well-known medication for acne vulgaris. Acne sometimes leaves dark spots on the skin, and we hypothesized that UP256 may be effective against hyperpigmentation-associated diseases. UP256 was treated for anti-melanogenesis and melanocyte dendrite formation in cultured normal human epidermal melanocytes as well as in the reconstituted skin and zebrafish models. Western blot analysis and glutathione S-transferase (GST)-pull down assays were used to evaluate the expression and interaction of enzymes related in melanin synthesis and transportation. The cellular tyrosinase activity and melanin content assay revealed that UP256 decreased melanin synthesis by regulating the expression of proteins related on melanogenesis including tyrosinase, TRP-1 and -2, and SOX9. UP256 also decreased dendrite formation in melanocytes via regulating the Rac/Cdc42/α-PAK signaling proteins, without cytotoxic effects. UP256 also inhibited ciliogenesis-dependent melanogenesis in normal human epidermal melanocytes. Furthermore, UP256 suppressed melanin contents in the zebrafish and the 3D human skin tissue model. All things taken together, UP256 inhibits melanin synthesis, dendrite formation, and primary cilium formation leading to the inhibition of melanogenesis.https://www.mdpi.com/1422-0067/21/15/5341UP256hyperpigmentationtyrosinasedendriteciliogenesismelanogenesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Min Cheol Kang Jae-Wook Lee Taek Hwan Lee Lalita Subedi Hussain M. Wahedi Seon-Gil Do Eunju Shin Eun-Yi Moon Sun Yeou Kim |
spellingShingle |
Min Cheol Kang Jae-Wook Lee Taek Hwan Lee Lalita Subedi Hussain M. Wahedi Seon-Gil Do Eunju Shin Eun-Yi Moon Sun Yeou Kim UP256 Inhibits Hyperpigmentation by Tyrosinase Expression/Dendrite Formation via Rho-Dependent Signaling and by Primary Cilium Formation in Melanocytes International Journal of Molecular Sciences UP256 hyperpigmentation tyrosinase dendrite ciliogenesis melanogenesis |
author_facet |
Min Cheol Kang Jae-Wook Lee Taek Hwan Lee Lalita Subedi Hussain M. Wahedi Seon-Gil Do Eunju Shin Eun-Yi Moon Sun Yeou Kim |
author_sort |
Min Cheol Kang |
title |
UP256 Inhibits Hyperpigmentation by Tyrosinase
Expression/Dendrite Formation via Rho-Dependent
Signaling and by Primary Cilium Formation
in Melanocytes |
title_short |
UP256 Inhibits Hyperpigmentation by Tyrosinase
Expression/Dendrite Formation via Rho-Dependent
Signaling and by Primary Cilium Formation
in Melanocytes |
title_full |
UP256 Inhibits Hyperpigmentation by Tyrosinase
Expression/Dendrite Formation via Rho-Dependent
Signaling and by Primary Cilium Formation
in Melanocytes |
title_fullStr |
UP256 Inhibits Hyperpigmentation by Tyrosinase
Expression/Dendrite Formation via Rho-Dependent
Signaling and by Primary Cilium Formation
in Melanocytes |
title_full_unstemmed |
UP256 Inhibits Hyperpigmentation by Tyrosinase
Expression/Dendrite Formation via Rho-Dependent
Signaling and by Primary Cilium Formation
in Melanocytes |
title_sort |
up256 inhibits hyperpigmentation by tyrosinase
expression/dendrite formation via rho-dependent
signaling and by primary cilium formation
in melanocytes |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-07-01 |
description |
Skin hyperpigmentation is generally characterized by increased synthesis and deposition of melanin in the skin. UP256, containing bakuchiol, is a well-known medication for acne vulgaris. Acne sometimes leaves dark spots on the skin, and we hypothesized that UP256 may be effective against hyperpigmentation-associated diseases. UP256 was treated for anti-melanogenesis and melanocyte dendrite formation in cultured normal human epidermal melanocytes as well as in the reconstituted skin and zebrafish models. Western blot analysis and glutathione S-transferase (GST)-pull down assays were used to evaluate the expression and interaction of enzymes related in melanin synthesis and transportation. The cellular tyrosinase activity and melanin content assay revealed that UP256 decreased melanin synthesis by regulating the expression of proteins related on melanogenesis including tyrosinase, TRP-1 and -2, and SOX9. UP256 also decreased dendrite formation in melanocytes via regulating the Rac/Cdc42/α-PAK signaling proteins, without cytotoxic effects. UP256 also inhibited ciliogenesis-dependent melanogenesis in normal human epidermal melanocytes. Furthermore, UP256 suppressed melanin contents in the zebrafish and the 3D human skin tissue model. All things taken together, UP256 inhibits melanin synthesis, dendrite formation, and primary cilium formation leading to the inhibition of melanogenesis. |
topic |
UP256 hyperpigmentation tyrosinase dendrite ciliogenesis melanogenesis |
url |
https://www.mdpi.com/1422-0067/21/15/5341 |
work_keys_str_mv |
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