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Semilicoisoflavone B induces oral cancer cell apoptosis by targeting claspin and ATR-Chk1 signaling pathways.
Hsieh, Ming-Ju; Lin, Chia-Chieh; Lo, Yu-Sheng; Chuang, Yi-Ching; Ho, Hsin-Yu; Chen, Mu-Kuan.
Afiliación
  • Hsieh MJ; Oral Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
  • Lin CC; Doctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
  • Lo YS; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
  • Chuang YC; Oral Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
  • Ho HY; Oral Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
  • Chen MK; Oral Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
Environ Toxicol ; 39(4): 2417-2428, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38197544
ABSTRACT
The prevalence of oral squamous cell carcinoma (OSCC) is increasing worldwide mainly due to poor oral hygiene and unrestricted lifestyle. Advanced-stage OSCC is associated with poor prognosis and a 5-year survival rate of only 30%-50%. The present study was designed to investigate the anticancer effect and mode of action of Glycyrrhiza-derived semilicoisoflavone B (SFB) in 5-fluorourasil (5FU)-resistant human OSCC cell lines. The study findings revealed that SFB significantly reduces OSCC cell viability and colony formation ability by arresting cell cycle at the G2/M and S phases and reducing the expressions of key cell cycle regulators including cyclin A, cyclin B, CDC2, and CDK2. The compound caused a significant induction in the percentage of nuclear condensation and apoptotic cells in OSCC. Regarding pro-apoptotic mode of action, SFB was found to increase Fas-associated death domain and death receptor 5 expressions and reduce decoy receptor 2 expression, indicating involvement of extrinsic pathway. Moreover, SFB was found to increase pro-apoptotic Bim expression and reduce anti-apoptotic Bcl-2 and Bcl-xL expressions, indicating involvement of intrinsic pathway. Moreover, SFB-mediated induction in cleaved caspases 3, 8, and 9 and cleaved poly(ADP-ribose) polymerase confirmed the induction of caspase-mediated apoptotic pathways. Regarding upstream signaling pathway, SFB was found to reduce extracellular signal regulated kinase 1/2 (ERK) phosphorylation to execute its pro-apoptotic activity. The Human Apoptotic Array findings revealed that SFB suppresses claspin expression, which in turn caused reduced phosphorylation of ATR, checkpoint kinase 1 (Chk1), Wee1, and CDC25C, indicating disruption of ATR-Chk1 signaling pathway by SFB. Taken together, these findings indicate that SFB acts as a potent anticancer compound against 5FU-resistant OSCC by modulating mitogen-activated protein kinase (MAPK) and ATR-Chk1 signaling pathways.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Flavonoides / Neoplasias de la Boca / Carcinoma de Células Escamosas Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Environ Toxicol Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Flavonoides / Neoplasias de la Boca / Carcinoma de Células Escamosas Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Environ Toxicol Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos