Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells
Zinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected mela...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8312 |
| _version_ | 1797413702428786688 |
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| author | Emil Rudolf Kamil Rudolf |
| author_facet | Emil Rudolf Kamil Rudolf |
| author_sort | Emil Rudolf |
| collection | DOAJ |
| description | Zinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected melanoma tissue explants with high or low intracellular free zinc. Zinc chelating agent TPEN at the concentration of 25 µM was employed during 48 h, which significantly reduced intracellular free zinc while decreasing melanoma cell proliferation, inducing G1/S arrest and cell damage leading to mitochondrial, caspase-dependent apoptosis. Chelation of free zinc was also associated with increased generation of superoxide in cell lines but not marked lysosomal membrane damage. Conversely, melanoma explant cultures mostly displayed time-dependent loss of lysosomal membrane integrity in the presence of slowly growing superoxide levels. Loss of free zinc-dependent p53 activity was similarly disparate in individual melanoma models. Surviving melanoma cells were arrested in the cell cycle, and varying proportions of them exhibited features characteristic of premature senescence, which increased in time despite zinc reloading. The present results show that melanoma cells with varying free zinc levels respond to its acute loss in a number of individual ways, reflecting activated mechanisms including oxidative stress, lysosomal damage, and p53 activity leading to heterogenous outcomes including cell death, transient, and/or permanent cell cycle arrest and premature senescence. |
| first_indexed | 2024-03-09T05:22:43Z |
| format | Article |
| id | doaj.art-f1d48ff135f24ac4bb9557a9ecb5dc53 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:22:43Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f1d48ff135f24ac4bb9557a9ecb5dc532023-12-03T12:39:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315831210.3390/ijms23158312Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma CellsEmil Rudolf0Kamil Rudolf1Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Zborovska 2089, 500 03 Hradec Kralove, Czech RepublicDepartment of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Zborovska 2089, 500 03 Hradec Kralove, Czech RepublicZinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected melanoma tissue explants with high or low intracellular free zinc. Zinc chelating agent TPEN at the concentration of 25 µM was employed during 48 h, which significantly reduced intracellular free zinc while decreasing melanoma cell proliferation, inducing G1/S arrest and cell damage leading to mitochondrial, caspase-dependent apoptosis. Chelation of free zinc was also associated with increased generation of superoxide in cell lines but not marked lysosomal membrane damage. Conversely, melanoma explant cultures mostly displayed time-dependent loss of lysosomal membrane integrity in the presence of slowly growing superoxide levels. Loss of free zinc-dependent p53 activity was similarly disparate in individual melanoma models. Surviving melanoma cells were arrested in the cell cycle, and varying proportions of them exhibited features characteristic of premature senescence, which increased in time despite zinc reloading. The present results show that melanoma cells with varying free zinc levels respond to its acute loss in a number of individual ways, reflecting activated mechanisms including oxidative stress, lysosomal damage, and p53 activity leading to heterogenous outcomes including cell death, transient, and/or permanent cell cycle arrest and premature senescence.https://www.mdpi.com/1422-0067/23/15/8312free zincmelanomachelationcell deathpremature senescence |
| spellingShingle | Emil Rudolf Kamil Rudolf Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells International Journal of Molecular Sciences free zinc melanoma chelation cell death premature senescence |
| title | Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells |
| title_full | Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells |
| title_fullStr | Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells |
| title_full_unstemmed | Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells |
| title_short | Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells |
| title_sort | induced zinc loss produces heterogenous biological responses in melanoma cells |
| topic | free zinc melanoma chelation cell death premature senescence |
| url | https://www.mdpi.com/1422-0067/23/15/8312 |
| work_keys_str_mv | AT emilrudolf inducedzinclossproducesheterogenousbiologicalresponsesinmelanomacells AT kamilrudolf inducedzinclossproducesheterogenousbiologicalresponsesinmelanomacells |