Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells
Zinc is one of the essential trace elements and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer a...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9457 |
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| author | Naoya Nakagawa Yutaka Fujisawa Huihui Xiang Hidemitsu Kitamura Keigo Nishida |
| author_facet | Naoya Nakagawa Yutaka Fujisawa Huihui Xiang Hidemitsu Kitamura Keigo Nishida |
| author_sort | Naoya Nakagawa |
| collection | DOAJ |
| description | Zinc is one of the essential trace elements and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, and the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added group than in the normal zinc intake group, and about half as many in the high-zinc-intake group as in the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. In this study, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and increases the transcription of granzyme B, one of the key molecules in tumor immunity. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:06:12Z |
| publishDate | 2023-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fb9bca3bd8214b36ab8bc8174b019acc2023-11-18T07:59:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411945710.3390/ijms24119457Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T CellsNaoya Nakagawa0Yutaka Fujisawa1Huihui Xiang2Hidemitsu Kitamura3Keigo Nishida4Laboratory of Immune Regulation, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, JapanFaculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, JapanDivision of Functional Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, JapanDivision of Functional Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, JapanLaboratory of Immune Regulation, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, JapanZinc is one of the essential trace elements and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, and the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added group than in the normal zinc intake group, and about half as many in the high-zinc-intake group as in the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. In this study, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and increases the transcription of granzyme B, one of the key molecules in tumor immunity.https://www.mdpi.com/1422-0067/24/11/9457zinccytotoxic T cellcolorectal cancergranzyme Btumor immunitycalcineurin |
| spellingShingle | Naoya Nakagawa Yutaka Fujisawa Huihui Xiang Hidemitsu Kitamura Keigo Nishida Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells International Journal of Molecular Sciences zinc cytotoxic T cell colorectal cancer granzyme B tumor immunity calcineurin |
| title | Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells |
| title_full | Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells |
| title_fullStr | Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells |
| title_full_unstemmed | Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells |
| title_short | Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells |
| title_sort | inhibitory effect of zinc on colorectal cancer by granzyme b transcriptional regulation in cytotoxic t cells |
| topic | zinc cytotoxic T cell colorectal cancer granzyme B tumor immunity calcineurin |
| url | https://www.mdpi.com/1422-0067/24/11/9457 |
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