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A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins.
Mendez-Callejas, Gina; Piñeros-Avila, Marco; Yosa-Reyes, Juvenal; Pestana-Nobles, Roberto; Torrenegra, Ruben; Camargo-Ubate, María F; Bello-Castro, Andrea E; Celis, Crispin A.
Afiliação
  • Mendez-Callejas G; Grupo 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, Colombia.
  • Piñeros-Avila M; Grupo 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, Colombia.
  • Yosa-Reyes J; Grupo de Investigación en Ciencias Exactas, Física y Naturales Aplicadas, Facultad de Ciencias Básicas y Biomédicas, Laboratorio de Simulación Molecular y Bioinformática, Universidad Simón Bolívar, Carrera 59 # 59-65, Barranquilla 080002, Colombia.
  • Pestana-Nobles R; Grupo de Investigación en Ciencias Exactas, Física y Naturales Aplicadas, Facultad de Ciencias Básicas y Biomédicas, Laboratorio de Simulación Molecular y Bioinformática, Universidad Simón Bolívar, Carrera 59 # 59-65, Barranquilla 080002, Colombia.
  • Torrenegra R; Grupo 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, Colombia.
  • Camargo-Ubate MF; Grupo 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, Colombia.
  • Bello-Castro AE; Grupo 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, Colombia.
  • Celis CA; Grupo de Investigación en Fitoquímica (GIFUJ), Departamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 # 40-62, Bogotá 1115511, Colombia.
Int J Mol Sci ; 24(20)2023 Oct 14.
Article em En | MEDLINE | ID: mdl-37894866
ABSTRACT
Chromolaena tacotana (Klatt) R. M. King and H. Rob (Ch. tacotana) contains bioactive flavonoids that may have antioxidant and/or anti-cancer properties. This study investigated the potential anti-cancer properties of a newly identified chalcone isolated from the inflorescences of the plant Chromolaena tacotana (Klatt) R. M. King and H. Rob (Ch. tacotana). The chalcone structure was determined using HPLC/MS (QTOF), UV, and NMR spectroscopy. The compound cytotoxicity and selectivity were evaluated on prostate, cervical, and breast cancer cell lines using the MTT assay. Apoptosis and autophagy induction were assessed through flow cytometry by detecting annexin V/7-AAD, active Casp3/7, and LC3B proteins. These results were supported by Western blot analysis. Mitochondrial effects on membrane potential, as well as levels of pro- and anti-apoptotic proteins were analyzed using flow cytometry, fluorescent microscopy, and Western blot analysis specifically on a triple-negative breast cancer (TNBC) cell line. Furthermore, molecular docking (MD) and molecular dynamics (MD) simulations were performed to evaluate the interaction between the compounds and pro-survival proteins. The compound identified as 2',3,4-trihydroxy-4',6'-dimethoxy chalcone inhibited the cancer cell line proliferation and induced apoptosis and autophagy. MDA-MB-231, a TNBC cell line, exhibited the highest sensitivity to the compound with good selectivity. This activity was associated with the regulation of mitochondrial membrane potential, activation of the pro-apoptotic proteins, and reduction of anti-apoptotic proteins, thereby triggering the intrinsic apoptotic pathway. The chalcone consistently interacted with anti-apoptotic proteins, particularly the Bcl-2 protein, throughout the simulation period. However, there was a noticeable conformational shift observed with the negative autophagy regulator mTOR protein. Future studies should focus on the molecular mechanisms underlying the anti-cancer potential of the new chalcone and other flavonoids from Ch. tacotana, particularly against predominant cancer cell types.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Chalcona / Chromolaena / Chalconas / Neoplasias de Mama Triplo Negativas Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Chalcona / Chromolaena / Chalconas / Neoplasias de Mama Triplo Negativas Idioma: En Ano de publicação: 2023 Tipo de documento: Article