NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases
NecroX-5 (NX-5) is a cell-permeable necrosis inhibitor with cytoprotective effects. Although it has been reported to inhibit lung and breast cancer metastasis by modulating migration, its therapeutic effect on melanoma metastasis is still unknown. In this study, we examined the anti-metastatic effec...
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MDPI AG
2021-06-01
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| Series: | Journal of Clinical Medicine |
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| author | Gue-Tae Moon Ji-Hyun Lee Sang-Hyun Jeong Song-Wan Jin Young-Min Park |
| author_facet | Gue-Tae Moon Ji-Hyun Lee Sang-Hyun Jeong Song-Wan Jin Young-Min Park |
| author_sort | Gue-Tae Moon |
| collection | DOAJ |
| description | NecroX-5 (NX-5) is a cell-permeable necrosis inhibitor with cytoprotective effects. Although it has been reported to inhibit lung and breast cancer metastasis by modulating migration, its therapeutic effect on melanoma metastasis is still unknown. In this study, we examined the anti-metastatic effect of NX-5 on melanoma cell lines and its related therapeutic mechanism. The anti-metastatic effect of NX-5 on melanoma cell lines was determined using a transwell migration assay. We performed a quantitative real-time polymerase chain reaction and western blot analysis to measure changes in the expression of mRNA and protein, respectively, for major mediators of Rho-family GTPases after NX-5 treatment in melanoma cells. In addition, after constructing the 3D melanoma model, the expression of Rho-family GTPases was measured by immunohistochemistry. NX-5 (10 μM and 20 μM) treatment significantly reduced melanoma cell migration (<i>p</i> < 0.01). Additionally, NX-5 (20 μM) treatment significantly decreased the mRNA and protein expression levels of Cdc42, Rac1, and RhoA in melanoma cells compared with the untreated group (<i>p</i> < 0.001 and <i>p</i> < 0.05, respectively). Immunohistochemistry for our 3D melanoma model showed that Cdc42, Rac1, and RhoA were constitutively expressed in the nuclei of melanoma cells of the untreated group, and NX-5 treatment decreased their expression. These results demonstrate that NX-5 can suppress melanoma metastasis by reducing the expression of Rho-family GTPases. |
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| language | English |
| last_indexed | 2024-03-10T10:04:50Z |
| publishDate | 2021-06-01 |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-a71c80462ccc4b9a85084f7b0f1809d62023-11-22T01:39:58ZengMDPI AGJournal of Clinical Medicine2077-03832021-06-011013279010.3390/jcm10132790NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPasesGue-Tae Moon0Ji-Hyun Lee1Sang-Hyun Jeong2Song-Wan Jin3Young-Min Park4Department of Biomedicine & Health Sciences, The Catholic University of Korea, #222 Banpo-daero, Seocho-gu, Seoul 06591, KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of Korea, #222 Banpo-daero, Seocho-gu, Seoul 06591, KoreaDepartment of Advanced Convergence Technology, Korea Polytechnic University, #237 Sangidaehak-ro, Siheung-si 15073, Gyeonggi-do, KoreaDepartment of Mechanical Engineering, Korea Polytechnic University, #237 Sangidaehak-ro, Siheung-si 15073, Gyeonggi-do, KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of Korea, #222 Banpo-daero, Seocho-gu, Seoul 06591, KoreaNecroX-5 (NX-5) is a cell-permeable necrosis inhibitor with cytoprotective effects. Although it has been reported to inhibit lung and breast cancer metastasis by modulating migration, its therapeutic effect on melanoma metastasis is still unknown. In this study, we examined the anti-metastatic effect of NX-5 on melanoma cell lines and its related therapeutic mechanism. The anti-metastatic effect of NX-5 on melanoma cell lines was determined using a transwell migration assay. We performed a quantitative real-time polymerase chain reaction and western blot analysis to measure changes in the expression of mRNA and protein, respectively, for major mediators of Rho-family GTPases after NX-5 treatment in melanoma cells. In addition, after constructing the 3D melanoma model, the expression of Rho-family GTPases was measured by immunohistochemistry. NX-5 (10 μM and 20 μM) treatment significantly reduced melanoma cell migration (<i>p</i> < 0.01). Additionally, NX-5 (20 μM) treatment significantly decreased the mRNA and protein expression levels of Cdc42, Rac1, and RhoA in melanoma cells compared with the untreated group (<i>p</i> < 0.001 and <i>p</i> < 0.05, respectively). Immunohistochemistry for our 3D melanoma model showed that Cdc42, Rac1, and RhoA were constitutively expressed in the nuclei of melanoma cells of the untreated group, and NX-5 treatment decreased their expression. These results demonstrate that NX-5 can suppress melanoma metastasis by reducing the expression of Rho-family GTPases.https://www.mdpi.com/2077-0383/10/13/2790NecroX-5melanomametastasisRho-family GTPaseCdc42Rac1 |
| spellingShingle | Gue-Tae Moon Ji-Hyun Lee Sang-Hyun Jeong Song-Wan Jin Young-Min Park NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases Journal of Clinical Medicine NecroX-5 melanoma metastasis Rho-family GTPase Cdc42 Rac1 |
| title | NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases |
| title_full | NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases |
| title_fullStr | NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases |
| title_full_unstemmed | NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases |
| title_short | NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases |
| title_sort | necrox 5 can suppress melanoma metastasis by reducing the expression of rho family gtpases |
| topic | NecroX-5 melanoma metastasis Rho-family GTPase Cdc42 Rac1 |
| url | https://www.mdpi.com/2077-0383/10/13/2790 |
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