Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma
Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of...
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2025-01-01
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| author | Angélica Luna-Nophal Fernando Díaz-Castillo Vanessa Izquierdo-Sánchez Jesús B. Velázquez-Fernández Mario Orozco-Morales Luis Lara-Mejía Johana Bernáldez-Sarabia Noemí Sánchez-Campos Oscar Arrieta José Díaz-Chávez Jorge-Ismael Castañeda-Sánchez Alexei-Fedorovish Licea-Navarro Saé Muñiz-Hernández |
| author_facet | Angélica Luna-Nophal Fernando Díaz-Castillo Vanessa Izquierdo-Sánchez Jesús B. Velázquez-Fernández Mario Orozco-Morales Luis Lara-Mejía Johana Bernáldez-Sarabia Noemí Sánchez-Campos Oscar Arrieta José Díaz-Chávez Jorge-Ismael Castañeda-Sánchez Alexei-Fedorovish Licea-Navarro Saé Muñiz-Hernández |
| author_sort | Angélica Luna-Nophal |
| collection | DOAJ |
| description | Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of marine snails have been demonstrated to be potential sources of novel anticancer molecules. This study analyzed the anticancer effects in vitro and in vivo of two peptides found in <i>C. californicus</i>. The effects of s-cal14.1b and s-cal14.2b on cell proliferation, apoptosis, and cytotoxicity were evaluated in 2D and 3D cultures of MPM-derived cells. Proteomics analysis of 3D cultures treated with conotoxins was performed to examine changes in expression or abundance. And the therapeutic effects of both conotoxins were evaluated in MPM mouse xenografts. s-cal14.1b and s-cal14.2b induced apoptosis and cytotoxicity in 2D and 3D cultures. However, only s-cal14.1b modified spheroid growth. Approximately 600 proteins exhibited important differential expression, which was more heterogeneous in H2452 vs MSTO-211H spheroids. The in silico protein functional analysis showed modifications in the biological pathways associated with carcinogenesis. CAPN1, LIMA1, ANXA6, HUWE1, PARP1 or PARP4 proteins could be potential cell targets for conotoxins and serve as biomarkers in MPM. Finally, we found that both conotoxins reduced the tumor mass in MPM xenografts; s-cal14.1b reached statistical significance. Based on these results, s-cal14.1b and s-cal14.2b conotoxins could be potential therapeutic drugs for MPM neoplasms with no apparent side effects on normal cells. |
| format | Article |
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| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Marine Drugs |
| spelling | doaj-art-f507dc4ba92f4ccaaf9b5746692846ca2025-01-24T13:39:33ZengMDPI AGMarine Drugs1660-33972025-01-012313210.3390/md23010032Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural MesotheliomaAngélica Luna-Nophal0Fernando Díaz-Castillo1Vanessa Izquierdo-Sánchez2Jesús B. Velázquez-Fernández3Mario Orozco-Morales4Luis Lara-Mejía5Johana Bernáldez-Sarabia6Noemí Sánchez-Campos7Oscar Arrieta8José Díaz-Chávez9Jorge-Ismael Castañeda-Sánchez10Alexei-Fedorovish Licea-Navarro11Saé Muñiz-Hernández12Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Ciudad de Mexico 04960, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada 22860, MexicoLaboratorio de Oncología Experimental, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de Mexico 14080, MexicoCONAHCyT-Investigador por Mexico, Ciudad de Mexico 14080, MexicoLaboratorio de Oncología Experimental, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de Mexico 14080, MexicoUnidad de Oncología Torácica, Instituto Nacional de Cancerología, Ciudad de Mexico 14080, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada 22860, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada 22860, MexicoLaboratorio de Oncología Experimental, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de Mexico 14080, MexicoLaboratorio de Oncologia Molecular y Biomarcadores, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de Mexico 14080, MexicoDepartamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, Ciudad de Mexico 04960, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada 22860, MexicoLaboratorio de Oncología Experimental, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de Mexico 14080, MexicoMalignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of marine snails have been demonstrated to be potential sources of novel anticancer molecules. This study analyzed the anticancer effects in vitro and in vivo of two peptides found in <i>C. californicus</i>. The effects of s-cal14.1b and s-cal14.2b on cell proliferation, apoptosis, and cytotoxicity were evaluated in 2D and 3D cultures of MPM-derived cells. Proteomics analysis of 3D cultures treated with conotoxins was performed to examine changes in expression or abundance. And the therapeutic effects of both conotoxins were evaluated in MPM mouse xenografts. s-cal14.1b and s-cal14.2b induced apoptosis and cytotoxicity in 2D and 3D cultures. However, only s-cal14.1b modified spheroid growth. Approximately 600 proteins exhibited important differential expression, which was more heterogeneous in H2452 vs MSTO-211H spheroids. The in silico protein functional analysis showed modifications in the biological pathways associated with carcinogenesis. CAPN1, LIMA1, ANXA6, HUWE1, PARP1 or PARP4 proteins could be potential cell targets for conotoxins and serve as biomarkers in MPM. Finally, we found that both conotoxins reduced the tumor mass in MPM xenografts; s-cal14.1b reached statistical significance. Based on these results, s-cal14.1b and s-cal14.2b conotoxins could be potential therapeutic drugs for MPM neoplasms with no apparent side effects on normal cells.https://www.mdpi.com/1660-3397/23/1/32pharmacological activitytherapeutic effectmass spectrometrymarine toxinsprotein markers |
| spellingShingle | Angélica Luna-Nophal Fernando Díaz-Castillo Vanessa Izquierdo-Sánchez Jesús B. Velázquez-Fernández Mario Orozco-Morales Luis Lara-Mejía Johana Bernáldez-Sarabia Noemí Sánchez-Campos Oscar Arrieta José Díaz-Chávez Jorge-Ismael Castañeda-Sánchez Alexei-Fedorovish Licea-Navarro Saé Muñiz-Hernández Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma Marine Drugs pharmacological activity therapeutic effect mass spectrometry marine toxins protein markers |
| title | Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma |
| title_full | Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma |
| title_fullStr | Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma |
| title_full_unstemmed | Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma |
| title_short | Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma |
| title_sort | preclinical efficacy and proteomic prediction of molecular targets for s cal14 1b and s cal14 2b conotoxins with antitumor capacity in xenografts of malignant pleural mesothelioma |
| topic | pharmacological activity therapeutic effect mass spectrometry marine toxins protein markers |
| url | https://www.mdpi.com/1660-3397/23/1/32 |
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