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Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect.
Katoh, Mizuki; Fujii, Takuto; Tabuchi, Yoshiaki; Shimizu, Takahiro; Sakai, Hideki.
Afiliación
  • Katoh M; Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
  • Fujii T; Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan. fujiitk@pha.u-toyama.ac.jp.
  • Tabuchi Y; Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama, 930-0194, Japan.
  • Shimizu T; Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
  • Sakai H; Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
J Physiol Sci ; 74(1): 23, 2024 Apr 01.
Article en En | MEDLINE | ID: mdl-38561668
ABSTRACT
Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Tiroides / Glicósidos Cardíacos Límite: Humans Idioma: En Revista: J Physiol Sci Asunto de la revista: FISIOLOGIA / TRAUMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Tiroides / Glicósidos Cardíacos Límite: Humans Idioma: En Revista: J Physiol Sci Asunto de la revista: FISIOLOGIA / TRAUMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón