Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction
LAH, an acetogenin from the Annonaceae family, has demonstrated antitumor activity in several cancer cell lines and in vivo models, where it reduced the tumor size and induced programmed cell death. We focused on the effects of LAH on mitochondrial dynamics, mTOR signaling, autophagy, and apoptosis...
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MDPI AG
2024-10-01
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| author | Izamary Delgado-Waldo Svetlana Dokudovskaya Yahir A. Loissell-Baltazar Eduardo Pérez-Arteaga Jossimar Coronel-Hernández Mariano Martínez-Vázquez Eloy Andrés Pérez-Yépez Alejandro Lopez-Saavedra Nadia Jacobo-Herrera Carlos Pérez Plasencia |
| author_facet | Izamary Delgado-Waldo Svetlana Dokudovskaya Yahir A. Loissell-Baltazar Eduardo Pérez-Arteaga Jossimar Coronel-Hernández Mariano Martínez-Vázquez Eloy Andrés Pérez-Yépez Alejandro Lopez-Saavedra Nadia Jacobo-Herrera Carlos Pérez Plasencia |
| author_sort | Izamary Delgado-Waldo |
| collection | DOAJ |
| description | LAH, an acetogenin from the Annonaceae family, has demonstrated antitumor activity in several cancer cell lines and in vivo models, where it reduced the tumor size and induced programmed cell death. We focused on the effects of LAH on mitochondrial dynamics, mTOR signaling, autophagy, and apoptosis in colorectal cancer (CRC) cells to explore its anticancer potential. Methods: CRC cells were treated with LAH, and its effects on mitochondrial respiration and glycolysis were measured using Seahorse XF technology. The changes in mitochondrial dynamics were observed through fluorescent imaging, while Western blot analysis was used to examine key autophagy and apoptosis markers. Results: LAH significantly inhibited mitochondrial complex I activity, inducing ATP depletion and a compensatory increase in glycolysis. This disruption caused mitochondrial fragmentation, a trigger for autophagy, as shown by increased LC3-II expression and mTOR suppression. Apoptosis was also confirmed through the cleavage of caspase-3, contributing to reduced cancer cell viability. Conclusions: LAH’s anticancer effects in CRC cells are driven by its disruption of mitochondrial function, triggering both autophagy and apoptosis. These findings highlight its potential as a therapeutic compound for further exploration in cancer treatment. |
| format | Article |
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| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-e25dedf5fe1b4b50b7245cfa7cd433c42025-08-20T01:47:42ZengMDPI AGCells2073-44092024-10-011319164910.3390/cells13191649Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy InductionIzamary Delgado-Waldo0Svetlana Dokudovskaya1Yahir A. Loissell-Baltazar2Eduardo Pérez-Arteaga3Jossimar Coronel-Hernández4Mariano Martínez-Vázquez5Eloy Andrés Pérez-Yépez6Alejandro Lopez-Saavedra7Nadia Jacobo-Herrera8Carlos Pérez Plasencia9Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Av. Vasco de Quiroga 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, MexicoCNRS UMR9018, Institut Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, FranceCNRS UMR9018, Institut Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, FranceUnidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Av. Vasco de Quiroga 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, Instituto Nacional Nacional de Cancerología, Av. San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México 14080, MexicoInstituto de Química, Universidad Nacional Autónoma de México, C. Exterior, C. Universitaria, Coyoacán, Ciudad de México 04510, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, Instituto Nacional Nacional de Cancerología, Av. San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México 14080, MexicoAdvanced Microscopy Applications Unit (ADMIRA), Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan, Ciudad de México 14080, MexicoUnidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Av. Vasco de Quiroga 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, Instituto Nacional Nacional de Cancerología, Av. San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México 14080, MexicoLAH, an acetogenin from the Annonaceae family, has demonstrated antitumor activity in several cancer cell lines and in vivo models, where it reduced the tumor size and induced programmed cell death. We focused on the effects of LAH on mitochondrial dynamics, mTOR signaling, autophagy, and apoptosis in colorectal cancer (CRC) cells to explore its anticancer potential. Methods: CRC cells were treated with LAH, and its effects on mitochondrial respiration and glycolysis were measured using Seahorse XF technology. The changes in mitochondrial dynamics were observed through fluorescent imaging, while Western blot analysis was used to examine key autophagy and apoptosis markers. Results: LAH significantly inhibited mitochondrial complex I activity, inducing ATP depletion and a compensatory increase in glycolysis. This disruption caused mitochondrial fragmentation, a trigger for autophagy, as shown by increased LC3-II expression and mTOR suppression. Apoptosis was also confirmed through the cleavage of caspase-3, contributing to reduced cancer cell viability. Conclusions: LAH’s anticancer effects in CRC cells are driven by its disruption of mitochondrial function, triggering both autophagy and apoptosis. These findings highlight its potential as a therapeutic compound for further exploration in cancer treatment.https://www.mdpi.com/2073-4409/13/19/1649laherradurinacetogeninscolon cancermitochondriaautophagyapoptosis |
| spellingShingle | Izamary Delgado-Waldo Svetlana Dokudovskaya Yahir A. Loissell-Baltazar Eduardo Pérez-Arteaga Jossimar Coronel-Hernández Mariano Martínez-Vázquez Eloy Andrés Pérez-Yépez Alejandro Lopez-Saavedra Nadia Jacobo-Herrera Carlos Pérez Plasencia Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction Cells laherradurin acetogenins colon cancer mitochondria autophagy apoptosis |
| title | Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction |
| title_full | Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction |
| title_fullStr | Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction |
| title_full_unstemmed | Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction |
| title_short | Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction |
| title_sort | laherradurin inhibits colorectal cancer cell growth by induction of mitochondrial dysfunction and autophagy induction |
| topic | laherradurin acetogenins colon cancer mitochondria autophagy apoptosis |
| url | https://www.mdpi.com/2073-4409/13/19/1649 |
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