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Blockade of CaV3 calcium channels and induction of G0/G1 cell cycle arrest in colon cancer cells by gossypol.
Lopez-Charcas, Osbaldo; Benouna, Oumnia; Lemoine, Roxane; Rosendo-Pineda, Margarita Jacaranda; Anguheven-Ledezma, Tonantzin Guadalupe; Sandoval-Vazquez, Lizeth; Gallegos-Gomez, Martin Leonardo; Robles-Martinez, Leticia; Herrera-Carrillo, Zazil; Ramírez-Aragón, Miguel; Alfaro, Ana; Chadet, Stéphanie; Ferro, Fabio; Besson, Pierre; Jiang, Lin-Hua; Velu, Sadanandan E; Guerrero-Hernandez, Agustín; Roger, Sébastien; Gomora, Juan Carlos.
Afiliación
  • Lopez-Charcas O; Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Benouna O; Université de Tours, Inserm U1327 ISCHEMIA 'Membrane Signalling and Inflammation in Reperfusion Injuries', Tours, France.
  • Lemoine R; Université de Tours, Inserm U1327 ISCHEMIA 'Membrane Signalling and Inflammation in Reperfusion Injuries', Tours, France.
  • Rosendo-Pineda MJ; Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Anguheven-Ledezma TG; Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Sandoval-Vazquez L; Department of Biochemistry, CINVESTAV, Mexico City, Mexico.
  • Gallegos-Gomez ML; Department of Biochemistry, CINVESTAV, Mexico City, Mexico.
  • Robles-Martinez L; Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Herrera-Carrillo Z; Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Ramírez-Aragón M; Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac, Mexico City, Mexico.
  • Alfaro A; Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Chadet S; Servicio de Anatomía Patológica, Hospital General de México 'Dr. Eduardo Liceaga', Mexico City, Mexico.
  • Ferro F; Université de Tours, Inserm U1327 ISCHEMIA 'Membrane Signalling and Inflammation in Reperfusion Injuries', Tours, France.
  • Besson P; Université de Tours, Inserm U1327 ISCHEMIA 'Membrane Signalling and Inflammation in Reperfusion Injuries', Tours, France.
  • Jiang LH; Université de Tours, Inserm U1327 ISCHEMIA 'Membrane Signalling and Inflammation in Reperfusion Injuries', Tours, France.
  • Velu SE; Université de Tours, Inserm U1327 ISCHEMIA 'Membrane Signalling and Inflammation in Reperfusion Injuries', Tours, France.
  • Guerrero-Hernandez A; Department of Physiology and Pathophysiology and Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Xinxiang Medical University, Xinxiang, China.
  • Roger S; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
  • Gomora JC; Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Br J Pharmacol ; 2024 Jul 31.
Article en En | MEDLINE | ID: mdl-39081110
ABSTRACT
BACKGROUND AND

PURPOSE:

Gastrointestinal tumours overexpress voltage-gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti-tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. EXPERIMENTAL

APPROACH:

Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch-clamp experiments. The anti-tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. KEY

RESULTS:

High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration- and use-dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down-regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. CONCLUSION AND IMPLICATIONS Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: México Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Br J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: México Pais de publicación: Reino Unido