Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis
Breast cancer (BC) is one of the most common cancers among women. Effective treatment requires precise tailoring to the genetic makeup of the cancer for improved efficacy. Numerous research studies have concentrated on natural compounds and their anti-breast cancer properties to improve the existing...
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MDPI AG
2024-02-01
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| Series: | Plants |
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| Online Access: | https://www.mdpi.com/2223-7747/13/5/570 |
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| author | Gina Mendez-Callejas Marco Piñeros-Avila Crispin A. Celis Ruben Torrenegra Anderson Espinosa-Benitez Roberto Pestana-Nobles Juvenal Yosa-Reyes |
| author_facet | Gina Mendez-Callejas Marco Piñeros-Avila Crispin A. Celis Ruben Torrenegra Anderson Espinosa-Benitez Roberto Pestana-Nobles Juvenal Yosa-Reyes |
| author_sort | Gina Mendez-Callejas |
| collection | DOAJ |
| description | Breast cancer (BC) is one of the most common cancers among women. Effective treatment requires precise tailoring to the genetic makeup of the cancer for improved efficacy. Numerous research studies have concentrated on natural compounds and their anti-breast cancer properties to improve the existing treatment options. <i>Chromolaena tacotana</i> (Klatt) R.M. King and H. Rob (<i>Ch</i>. <i>tacotana)</i> is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant’s inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from <i>Ch. tacotana</i> inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and Western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between chalcone and various anti-apoptotic proteins, including the mTOR protein. Chalcone was identified as 2′,4-dihydroxy-4′,6′-dimethoxy-chalcone (DDC). This compound demonstrated a selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study detected the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to the BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in BC cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents, like the hydroxy-methylated flavonoids from <i>Ch. tacotana</i>. |
| first_indexed | 2024-04-25T00:21:48Z |
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| institution | Directory Open Access Journal |
| issn | 2223-7747 |
| language | English |
| last_indexed | 2024-04-25T00:21:48Z |
| publishDate | 2024-02-01 |
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| series | Plants |
| spelling | doaj.art-0b9533d8da7c490b81d3b7ece70c94962024-03-12T16:52:30ZengMDPI AGPlants2223-77472024-02-0113557010.3390/plants13050570Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial ApoptosisGina Mendez-Callejas0Marco Piñeros-Avila1Crispin A. Celis2Ruben Torrenegra3Anderson Espinosa-Benitez4Roberto Pestana-Nobles5Juvenal Yosa-Reyes6Grupo de Investigaciones Biomédicas y de Genética Humana Aplicada (GIBGA), Laboratorio de Biología Celular y Molecular, Facultad de Ciencias de la Salud, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A.), Calle 222 #55-37, Bogotá 111166, ColombiaGrupo de Investigaciones Biomédicas y de Genética Humana Aplicada (GIBGA), Laboratorio de Biología Celular y Molecular, Facultad de Ciencias de la Salud, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A.), Calle 222 #55-37, Bogotá 111166, ColombiaGrupo de Investigación en Fitoquímica (GIFUJ), Departamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 #40-62, Bogotá 111321, ColombiaGrupo de Investigación en Productos Naturales de la U.D.C.A. (PRONAUDCA), Laboratorio de Productos Naturales, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A.), Calle 222 #55-37, Bogotá 111166, ColombiaGrupo de Investigaciones Biomédicas y de Genética Humana Aplicada (GIBGA), Laboratorio de Biología Celular y Molecular, Facultad de Ciencias de la Salud, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A.), Calle 222 #55-37, Bogotá 111166, ColombiaGrupo de Investigación en Ciencias Exactas, Física y Naturales Aplicadas, Laboratorio de Simulación Molecular y Bioinformática, Facultad de Ciencias Básicas y Biomédicas, Universidad Simón Bolívar, Carrera 59 #59-65, Barranquilla 080002, ColombiaGrupo de Investigación en Ciencias Exactas, Física y Naturales Aplicadas, Laboratorio de Simulación Molecular y Bioinformática, Facultad de Ciencias Básicas y Biomédicas, Universidad Simón Bolívar, Carrera 59 #59-65, Barranquilla 080002, ColombiaBreast cancer (BC) is one of the most common cancers among women. Effective treatment requires precise tailoring to the genetic makeup of the cancer for improved efficacy. Numerous research studies have concentrated on natural compounds and their anti-breast cancer properties to improve the existing treatment options. <i>Chromolaena tacotana</i> (Klatt) R.M. King and H. Rob (<i>Ch</i>. <i>tacotana)</i> is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant’s inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from <i>Ch. tacotana</i> inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and Western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between chalcone and various anti-apoptotic proteins, including the mTOR protein. Chalcone was identified as 2′,4-dihydroxy-4′,6′-dimethoxy-chalcone (DDC). This compound demonstrated a selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study detected the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to the BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in BC cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents, like the hydroxy-methylated flavonoids from <i>Ch. tacotana</i>.https://www.mdpi.com/2223-7747/13/5/570<i>Chromolaena tacotana</i>chalconebreast cancerintrinsic apoptosisautophagy |
| spellingShingle | Gina Mendez-Callejas Marco Piñeros-Avila Crispin A. Celis Ruben Torrenegra Anderson Espinosa-Benitez Roberto Pestana-Nobles Juvenal Yosa-Reyes Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis Plants <i>Chromolaena tacotana</i> chalcone breast cancer intrinsic apoptosis autophagy |
| title | Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis |
| title_full | Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis |
| title_fullStr | Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis |
| title_full_unstemmed | Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis |
| title_short | Natural 2′,4-Dihydroxy-4′,6′-dimethoxy Chalcone Isolated from <i>Chromolaena tacotana</i> Inhibits Breast Cancer Cell Growth through Autophagy and Mitochondrial Apoptosis |
| title_sort | natural 2 4 dihydroxy 4 6 dimethoxy chalcone isolated from i chromolaena tacotana i inhibits breast cancer cell growth through autophagy and mitochondrial apoptosis |
| topic | <i>Chromolaena tacotana</i> chalcone breast cancer intrinsic apoptosis autophagy |
| url | https://www.mdpi.com/2223-7747/13/5/570 |
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