Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex
IntroductionBreast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TN...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1341766/full |
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| author | Dayan A. Carrión-Estrada Arturo Aguilar-Rojas Sara Huerta-Yepez Mayra Montecillo-Aguado Martiniano Bello Arturo Rojo-Domínguez Elena Arechaga-Ocampo Paola Briseño-Díaz Marco Antonio Meraz-Ríos María del Rocío Thompson-Bonilla Rosaura Hernández-Rivas Miguel Vargas |
| author_facet | Dayan A. Carrión-Estrada Arturo Aguilar-Rojas Sara Huerta-Yepez Mayra Montecillo-Aguado Martiniano Bello Arturo Rojo-Domínguez Elena Arechaga-Ocampo Paola Briseño-Díaz Marco Antonio Meraz-Ríos María del Rocío Thompson-Bonilla Rosaura Hernández-Rivas Miguel Vargas |
| author_sort | Dayan A. Carrión-Estrada |
| collection | DOAJ |
| description | IntroductionBreast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TNBC and radioresistant TNBC cells. These compounds were chosen for their ability to stabilize the complex formed by the overactivated form of K-Ras4BG13D and its membrane transporter (PDE6δ).MethodsThe antitumor potential of C14 and P8 was assessed using TNBC cell lines, MDA-MB-231, and the radioresistant derivative MDA-MB-231RR, both carrying the K-Ras4B>
G13D mutation. We investigated the compounds' effects on K-Ras signaling pathways, cell viability, and tumor growth in vivo.ResultsWestern blotting analysis determined the negative impact of C14 and P8 on the activation of mutant K-Ras signaling pathways in MDA-MB-231 and MDA-MB-231RR cells. Proliferation assays demonstrated their efficacy as cytotoxic agents against K-RasG13D mutant cancer cells and in inducing apoptosis. Clonogenic assays proven their ability to inhibit TNBC and radioresistant TNBC cell clonogenicity. In In vivo studies, C14 and P8 inhibited tumor growth and reduced proliferation, angiogenesis, and cell cycle progression markers.DiscussionThese findings suggest that C14 and P8 could serve as promising adjuvant treatments for TNBC, particularly for non-responders to standard therapies. By targeting overactivated K-Ras and its membrane transporter, these compounds offer potential therapeutic benefits against TNBC, including its radioresistant form. Further research and clinical trials are warranted to validate their efficacy and safety as novel TNBC treatments. |
| first_indexed | 2024-04-24T21:59:46Z |
| format | Article |
| id | doaj.art-3442ecfa356b428cbc9771756dc5d80a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-24T21:59:46Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3442ecfa356b428cbc9771756dc5d80a2024-03-20T12:41:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-03-011410.3389/fonc.2024.13417661341766Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complexDayan A. Carrión-Estrada0Arturo Aguilar-Rojas1Sara Huerta-Yepez2Mayra Montecillo-Aguado3Martiniano Bello4Arturo Rojo-Domínguez5Elena Arechaga-Ocampo6Paola Briseño-Díaz7Marco Antonio Meraz-Ríos8María del Rocío Thompson-Bonilla9Rosaura Hernández-Rivas10Miguel Vargas11Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-I.P.N.), Mexico City, MexicoMedical Research Unit in Reproductive Medicine, Mexican Social Security Institute (IMSS), High Specialty Medical Unit in Gynecology and Obstetrics No. 4 Dr. Luis Castelazo Ayala, Mexico City, MexicoResearch Unit in Oncological Diseases, Children’s Hospital of Mexico Federico Gómez, Mexico City, MexicoResearch Unit in Oncological Diseases, Children’s Hospital of Mexico Federico Gómez, Mexico City, MexicoLaboratory for the Design and Development of New Drugs and Biotechnological Innovation, Higher School of Medicine, National Polytechnic Institute, Mexico City, MexicoDepartment of Natural Sciences, Metropolitan Autonomous University Cuajimalpa Unit, Mexico City, MexicoDepartment of Natural Sciences, Metropolitan Autonomous University Cuajimalpa Unit, Mexico City, MexicoDepartment of Biochemistry of the Faculty of Medicine of the National Autonomous University of Mexico (UNAM), Mexico City, MexicoDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-I.P.N.), Mexico City, MexicoBiomedical and Transnational Research, Genomic Medicine Laboratory, Hospital 1° de Octubre, Institute of Security and Social Services of State Workers (ISSSTE), Mexico City, MexicoDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-I.P.N.), Mexico City, MexicoDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-I.P.N.), Mexico City, MexicoIntroductionBreast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TNBC and radioresistant TNBC cells. These compounds were chosen for their ability to stabilize the complex formed by the overactivated form of K-Ras4BG13D and its membrane transporter (PDE6δ).MethodsThe antitumor potential of C14 and P8 was assessed using TNBC cell lines, MDA-MB-231, and the radioresistant derivative MDA-MB-231RR, both carrying the K-Ras4B> G13D mutation. We investigated the compounds' effects on K-Ras signaling pathways, cell viability, and tumor growth in vivo.ResultsWestern blotting analysis determined the negative impact of C14 and P8 on the activation of mutant K-Ras signaling pathways in MDA-MB-231 and MDA-MB-231RR cells. Proliferation assays demonstrated their efficacy as cytotoxic agents against K-RasG13D mutant cancer cells and in inducing apoptosis. Clonogenic assays proven their ability to inhibit TNBC and radioresistant TNBC cell clonogenicity. In In vivo studies, C14 and P8 inhibited tumor growth and reduced proliferation, angiogenesis, and cell cycle progression markers.DiscussionThese findings suggest that C14 and P8 could serve as promising adjuvant treatments for TNBC, particularly for non-responders to standard therapies. By targeting overactivated K-Ras and its membrane transporter, these compounds offer potential therapeutic benefits against TNBC, including its radioresistant form. Further research and clinical trials are warranted to validate their efficacy and safety as novel TNBC treatments.https://www.frontiersin.org/articles/10.3389/fonc.2024.1341766/fullK-Ras4BPDE6δbreast cancertriple negative breast cancer (TNBC)radioresistantantitumor compounds |
| spellingShingle | Dayan A. Carrión-Estrada Arturo Aguilar-Rojas Sara Huerta-Yepez Mayra Montecillo-Aguado Martiniano Bello Arturo Rojo-Domínguez Elena Arechaga-Ocampo Paola Briseño-Díaz Marco Antonio Meraz-Ríos María del Rocío Thompson-Bonilla Rosaura Hernández-Rivas Miguel Vargas Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex Frontiers in Oncology K-Ras4B PDE6δ breast cancer triple negative breast cancer (TNBC) radioresistant antitumor compounds |
| title | Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex |
| title_full | Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex |
| title_fullStr | Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex |
| title_full_unstemmed | Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex |
| title_short | Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex |
| title_sort | antineoplastic effect of compounds c14 and p8 on tnbc and radioresistant tnbc cells by stabilizing the k ras4bg13d pde6δ complex |
| topic | K-Ras4B PDE6δ breast cancer triple negative breast cancer (TNBC) radioresistant antitumor compounds |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1341766/full |
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