Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1
Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer worldwide. In addition, metastasis directly causes up to 90% of all CRC deaths, highlighting the metastatic burden of the disease. Biomarkers such as S100A4 and MACC1 aid in identifying patients with a high risk of metas...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1179 |
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| author | Paul Curtis Schöpe Viktoria Zinnow Muhammad Ahtisham Ishfaq Janice Smith Pia Herrmann Robert H. Shoemaker Wolfgang Walther Ulrike Stein |
| author_facet | Paul Curtis Schöpe Viktoria Zinnow Muhammad Ahtisham Ishfaq Janice Smith Pia Herrmann Robert H. Shoemaker Wolfgang Walther Ulrike Stein |
| author_sort | Paul Curtis Schöpe |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer worldwide. In addition, metastasis directly causes up to 90% of all CRC deaths, highlighting the metastatic burden of the disease. Biomarkers such as S100A4 and MACC1 aid in identifying patients with a high risk of metastasis formation. High expression of S100A4 or MACC1 and to a greater extent the combination of both biomarkers is a predictor for metastasis and poor patient survival in CRC. MACC1 is a tumor-initiating and metastasis-promoting oncogene, whereas S100A4 has not been shown to initiate tumor formation but can, nevertheless, promote malignant tumor growth and metastasis formation. Cantharidin is a natural drug extracted from various blister beetle species, and its demethylated analogue norcantharidin has been shown in several studies to have an anti-cancer and anti-metastatic effect in different cancer entities such as CRC, breast cancer, and lung cancer. The impact of the natural compound cantharidin and norcantharidin on S100A4 and MACC1 gene expression, cancer cell migration, motility, and colony formation in vitro was tested. Here, for the first time, we have demonstrated that cantharidin and norcantharidin are transcriptional inhibitors of S100A4 and MACC1 mRNA expression, protein expression, and motility in CRC cells. Our results clearly indicate that cantharidin and, to a lesser extent, its analogue norcantharidin are promising compounds for efficient anti-metastatic therapy targeting the metastasis-inducing genes S100A4 and MACC1 for personalized medicine for cancer patients. |
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| language | English |
| last_indexed | 2024-03-09T12:24:31Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1e9467841d7f48f3a0874f2a1c9e23bd2023-11-30T22:36:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242117910.3390/ijms24021179Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1Paul Curtis Schöpe0Viktoria Zinnow1Muhammad Ahtisham Ishfaq2Janice Smith3Pia Herrmann4Robert H. Shoemaker5Wolfgang Walther6Ulrike Stein7Experimental and Clinical Research Center, Charité—Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, GermanyExperimental and Clinical Research Center, Charité—Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, GermanyExperimental and Clinical Research Center, Charité—Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, GermanyExperimental and Clinical Research Center, Charité—Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, GermanyExperimental and Clinical Research Center, Charité—Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, GermanyChemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USAExperimental and Clinical Research Center, Charité—Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, GermanyExperimental and Clinical Research Center, Charité—Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, GermanyColorectal cancer (CRC) is the third most prevalent and second deadliest cancer worldwide. In addition, metastasis directly causes up to 90% of all CRC deaths, highlighting the metastatic burden of the disease. Biomarkers such as S100A4 and MACC1 aid in identifying patients with a high risk of metastasis formation. High expression of S100A4 or MACC1 and to a greater extent the combination of both biomarkers is a predictor for metastasis and poor patient survival in CRC. MACC1 is a tumor-initiating and metastasis-promoting oncogene, whereas S100A4 has not been shown to initiate tumor formation but can, nevertheless, promote malignant tumor growth and metastasis formation. Cantharidin is a natural drug extracted from various blister beetle species, and its demethylated analogue norcantharidin has been shown in several studies to have an anti-cancer and anti-metastatic effect in different cancer entities such as CRC, breast cancer, and lung cancer. The impact of the natural compound cantharidin and norcantharidin on S100A4 and MACC1 gene expression, cancer cell migration, motility, and colony formation in vitro was tested. Here, for the first time, we have demonstrated that cantharidin and norcantharidin are transcriptional inhibitors of S100A4 and MACC1 mRNA expression, protein expression, and motility in CRC cells. Our results clearly indicate that cantharidin and, to a lesser extent, its analogue norcantharidin are promising compounds for efficient anti-metastatic therapy targeting the metastasis-inducing genes S100A4 and MACC1 for personalized medicine for cancer patients.https://www.mdpi.com/1422-0067/24/2/1179colorectal cancermetastasisS100A4MACC1cantharidinnorcantharidin |
| spellingShingle | Paul Curtis Schöpe Viktoria Zinnow Muhammad Ahtisham Ishfaq Janice Smith Pia Herrmann Robert H. Shoemaker Wolfgang Walther Ulrike Stein Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1 International Journal of Molecular Sciences colorectal cancer metastasis S100A4 MACC1 cantharidin norcantharidin |
| title | Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1 |
| title_full | Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1 |
| title_fullStr | Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1 |
| title_full_unstemmed | Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1 |
| title_short | Cantharidin and Its Analogue Norcantharidin Inhibit Metastasis—Inducing Genes S100A4 and MACC1 |
| title_sort | cantharidin and its analogue norcantharidin inhibit metastasis inducing genes s100a4 and macc1 |
| topic | colorectal cancer metastasis S100A4 MACC1 cantharidin norcantharidin |
| url | https://www.mdpi.com/1422-0067/24/2/1179 |
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