Melanosomal localization is required for GIF‐2115/2250 to inhibit melanogenesis in B16F10 melanoma cells
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Wiley
2024
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| author | Ayumi Sakurai Kyoka Kawaguchi Miyu Watanabe Sayaka Okajima Saho Furukawa Kenichi Koga Kentaro Oh‐Hashi Yoko Hirata Kyoji Furuta Hiroshi Takemori |
| author_facet | Ayumi Sakurai Kyoka Kawaguchi Miyu Watanabe Sayaka Okajima Saho Furukawa Kenichi Koga Kentaro Oh‐Hashi Yoko Hirata Kyoji Furuta Hiroshi Takemori Ayumi Sakurai Kyoka Kawaguchi Miyu Watanabe Sayaka Okajima Saho Furukawa Kenichi Koga Kentaro Oh‐Hashi Yoko Hirata Kyoji Furuta Hiroshi Takemori |
| collection | Wiley Open Access |
| contents | Melanosomal localization is required for GIF‐2115/2250 to inhibit melanogenesis in B16F10 melanoma cells Ayumi Sakurai Kyoka Kawaguchi Miyu Watanabe Sayaka Okajima Saho Furukawa Kenichi Koga Kentaro Oh‐Hashi Yoko Hirata Kyoji Furuta Hiroshi Takemori International Journal of Cosmetic Science AbstractObjectiveTyrosinase inhibitors suppress melanogenesis in melanocytes. During a screening for tyrosinase inhibitors, however, we noticed some discrepancies in inhibitory efficacies between melanocytes and in vitro assays. The compound (S)‐N‐{3‐[4‐(dimethylamino)phenyl]propyl}‐N‐methyl‐indan‐1‐amine (GIF‐2115) exerts antioxidative stress activity upon accumulation in late endosomes and lysosomes. GIF‐2115 was also identified as a potent antimelanogenic reagent in B16F10 mouse melanoma cells. GIF‐2115 inhibited the activity of mushroom tyrosinase and the lysates of B16F10 cells. However, structure–activity relationship studies indicated that GIF‐2238, which lacks the benzene ring in the aminoindan structure of GIF‐2115, inhibited tyrosinase activity in vitro but did not inhibit melanogenesis in B16F10 cells. The aim of the present study is to show the importance of the intracellular distribution of tyrosinase inhibitors in exerting their antimelanogenic activity in melanocytes.MethodsThe intracellular distribution of compounds was monitored by linking with the fluorescent group of 7‐nitro‐2,1,3‐benzoxadiazole (NBD). To mislocalize GIF‐2115 to mitochondria, the mitochondria‐preferring fluoroprobe ATTO565 was used.ResultsWe reconfirmed the localization of GIF‐2250 (GIF‐2115‐NBD) not only to matured but also to early‐stage melanosomes. Although GIF‐2286 (GIF‐2238‐NBD) maintained tyrosinase inhibitory activity, it did not show specific intracellular localization. Moreover, when GIF‐2115 was linked with ATTO565, the resultant compound GIF‐2265 did not inhibit melanogenesis in B16F10 cells, despite its strong tyrosinase inhibitory activity.ConclusionThese results suggest that melanosomal localization is essential for the antimelanogenic activity of GIF‐2115, and GIF‐2115 derivatives may be new guides for drugs to endosomes and lysosomes as well as melanosomes. 10.1111/ics.12949 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/ics.12949 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_ics_12949 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Melanosomal localization is required for GIF‐2115/2250 to inhibit melanogenesis in B16F10 melanoma cells Ayumi Sakurai Kyoka Kawaguchi Miyu Watanabe Sayaka Okajima Saho Furukawa Kenichi Koga Kentaro Oh‐Hashi Yoko Hirata Kyoji Furuta Hiroshi Takemori International Journal of Cosmetic Science Melanosomal localization is required for GIF‐2115/2250 to inhibit melanogenesis in B16F10 melanoma cells Ayumi Sakurai Kyoka Kawaguchi Miyu Watanabe Sayaka Okajima Saho Furukawa Kenichi Koga Kentaro Oh‐Hashi Yoko Hirata Kyoji Furuta Hiroshi Takemori International Journal of Cosmetic Science AbstractObjectiveTyrosinase inhibitors suppress melanogenesis in melanocytes. During a screening for tyrosinase inhibitors, however, we noticed some discrepancies in inhibitory efficacies between melanocytes and in vitro assays. The compound (S)‐N‐{3‐[4‐(dimethylamino)phenyl]propyl}‐N‐methyl‐indan‐1‐amine (GIF‐2115) exerts antioxidative stress activity upon accumulation in late endosomes and lysosomes. GIF‐2115 was also identified as a potent antimelanogenic reagent in B16F10 mouse melanoma cells. GIF‐2115 inhibited the activity of mushroom tyrosinase and the lysates of B16F10 cells. However, structure–activity relationship studies indicated that GIF‐2238, which lacks the benzene ring in the aminoindan structure of GIF‐2115, inhibited tyrosinase activity in vitro but did not inhibit melanogenesis in B16F10 cells. The aim of the present study is to show the importance of the intracellular distribution of tyrosinase inhibitors in exerting their antimelanogenic activity in melanocytes.MethodsThe intracellular distribution of compounds was monitored by linking with the fluorescent group of 7‐nitro‐2,1,3‐benzoxadiazole (NBD). To mislocalize GIF‐2115 to mitochondria, the mitochondria‐preferring fluoroprobe ATTO565 was used.ResultsWe reconfirmed the localization of GIF‐2250 (GIF‐2115‐NBD) not only to matured but also to early‐stage melanosomes. Although GIF‐2286 (GIF‐2238‐NBD) maintained tyrosinase inhibitory activity, it did not show specific intracellular localization. Moreover, when GIF‐2115 was linked with ATTO565, the resultant compound GIF‐2265 did not inhibit melanogenesis in B16F10 cells, despite its strong tyrosinase inhibitory activity.ConclusionThese results suggest that melanosomal localization is essential for the antimelanogenic activity of GIF‐2115, and GIF‐2115 derivatives may be new guides for drugs to endosomes and lysosomes as well as melanosomes. 10.1111/ics.12949 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Melanosomal localization is required for GIF‐2115/2250 to inhibit melanogenesis in B16F10 melanoma cells |
| topic | International Journal of Cosmetic Science |
| url | https://onlinelibrary.wiley.com/doi/10.1111/ics.12949 |