Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk
Melanoma, the malignancy originating from pigment-producing melanocytes, is the most aggressive form of skin cancer and has a poor prognosis once the disease starts to metastasize. The process of melanin synthesis generates an immunosuppressive and mutagenic environment, and can increase melanoma ce...
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2021-05-01
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| author | Małgorzata Pawlikowska Tomasz Jędrzejewski Andrzej T. Slominski Anna A. Brożyna Sylwia Wrotek |
| author_facet | Małgorzata Pawlikowska Tomasz Jędrzejewski Andrzej T. Slominski Anna A. Brożyna Sylwia Wrotek |
| author_sort | Małgorzata Pawlikowska |
| collection | DOAJ |
| description | Melanoma, the malignancy originating from pigment-producing melanocytes, is the most aggressive form of skin cancer and has a poor prognosis once the disease starts to metastasize. The process of melanin synthesis generates an immunosuppressive and mutagenic environment, and can increase melanoma cell resistance to different treatment modalities, including chemo-, radio- or photodynamic therapy. Recently, we have shown that the presence of melanin pigment inhibits the melanoma cell response to bioactive components of <i>Coriolus versicolor</i> (CV) Chinese fungus. Herein, using the same human melanoma cell line in which the level of pigmentation can be controlled by the L-tyrosine concentration in culture medium, we tested the effect of suppression of melanogenesis on the melanoma cell response to CV extract and investigated the cell death pathway induced by fungus extract in sensitized melanoma cells. Our data showed that susceptibility to CV-induced melanoma cell death is significantly increased after cell depigmentation. To the best of our knowledge, we are the first to demonstrate that CV extract can induce RIPK1/RIPK3/MLKL-mediated necroptosis in depigmented melanoma cells. Moreover, using the co-culture system, we showed that inhibition of the tyrosinase activity in melanoma cells modulates cytokine expression in co-cultured mononuclear cells, indicating that depigmentation of melanoma cells may activate immune cells and thereby influence a host anticancer response. |
| first_indexed | 2024-03-10T10:58:42Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:58:42Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8ecde85a657e47978a7609afa95cf4322023-11-21T21:40:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211573510.3390/ijms22115735Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell CrosstalkMałgorzata Pawlikowska0Tomasz Jędrzejewski1Andrzej T. Slominski2Anna A. Brożyna3Sylwia Wrotek4Department of Immunology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, PolandDepartment of Immunology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, PolandDepartment of Dermatology, Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Human Biology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, PolandDepartment of Immunology, Faculty of Biology and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Toruń, PolandMelanoma, the malignancy originating from pigment-producing melanocytes, is the most aggressive form of skin cancer and has a poor prognosis once the disease starts to metastasize. The process of melanin synthesis generates an immunosuppressive and mutagenic environment, and can increase melanoma cell resistance to different treatment modalities, including chemo-, radio- or photodynamic therapy. Recently, we have shown that the presence of melanin pigment inhibits the melanoma cell response to bioactive components of <i>Coriolus versicolor</i> (CV) Chinese fungus. Herein, using the same human melanoma cell line in which the level of pigmentation can be controlled by the L-tyrosine concentration in culture medium, we tested the effect of suppression of melanogenesis on the melanoma cell response to CV extract and investigated the cell death pathway induced by fungus extract in sensitized melanoma cells. Our data showed that susceptibility to CV-induced melanoma cell death is significantly increased after cell depigmentation. To the best of our knowledge, we are the first to demonstrate that CV extract can induce RIPK1/RIPK3/MLKL-mediated necroptosis in depigmented melanoma cells. Moreover, using the co-culture system, we showed that inhibition of the tyrosinase activity in melanoma cells modulates cytokine expression in co-cultured mononuclear cells, indicating that depigmentation of melanoma cells may activate immune cells and thereby influence a host anticancer response.https://www.mdpi.com/1422-0067/22/11/5735melanomamelanogenesispigmentation<i>Coriolus versicolor</i> extractco-culture<span style="font-variant: small-caps">d</span>-penicillamine |
| spellingShingle | Małgorzata Pawlikowska Tomasz Jędrzejewski Andrzej T. Slominski Anna A. Brożyna Sylwia Wrotek Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk International Journal of Molecular Sciences melanoma melanogenesis pigmentation <i>Coriolus versicolor</i> extract co-culture <span style="font-variant: small-caps">d</span>-penicillamine |
| title | Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk |
| title_full | Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk |
| title_fullStr | Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk |
| title_full_unstemmed | Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk |
| title_short | Pigmentation Levels Affect Melanoma Responses to <i>Coriolus versicolor</i> Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk |
| title_sort | pigmentation levels affect melanoma responses to i coriolus versicolor i extract and play a crucial role in melanoma mononuclear cell crosstalk |
| topic | melanoma melanogenesis pigmentation <i>Coriolus versicolor</i> extract co-culture <span style="font-variant: small-caps">d</span>-penicillamine |
| url | https://www.mdpi.com/1422-0067/22/11/5735 |
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