Your browser doesn't support javascript.
loading
Vismodegib Potentiates Marine Antimicrobial Peptide Tilapia Piscidin 4-Induced Cytotoxicity in Human Non-Small Cell Lung Cancer Cells.
Yeh, Wei-Chen; Tu, Yun-Chieh; Chien, Tzu-Cheng; Hsu, Pei-Ling; Lee, Chu-Wan; Wu, Shih-Ying; Pan, Bo-Syong; Yu, Hsin-Hsien; Su, Bor-Chyuan.
Afiliación
  • Yeh WC; School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • Tu YC; School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • Chien TC; School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • Hsu PL; Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
  • Lee CW; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan.
  • Wu SY; Department of Nursing, National Tainan Junior College of Nursing, 78, Section 2, Minzu Road, West Central District, Tainan, 70007, Taiwan.
  • Pan BS; Department of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC, 27157, USA.
  • Yu HH; Department of Pathology, Duke University School of Medicine, Durham, NC27710, USA.
  • Su BC; Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Probiotics Antimicrob Proteins ; 2024 May 14.
Article en En | MEDLINE | ID: mdl-38743208
ABSTRACT
Non-small cell lung cancer (NSCLC) is a common cancer with several accepted treatments, such as chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and immune checkpoint inhibitors. Nevertheless, NSCLC cells often become insensitive to these treatments, and therapeutic resistance is a major reason NSCLC still has a high mortality rate. The induction of therapeutic resistance in NSCLC often involves hedgehog, and suppression of hedgehog can increase NSCLC cell sensitivity to several conventional therapies. In our previous work, we demonstrated that the marine antimicrobial peptide tilapia piscidin 4 (TP4) exhibits potent anti-NSCLC activity in both EGFR-WT and EGFR-mutant NSCLC cells. Here, we sought to further explore whether hedgehog might influence the sensitivity of NSCLC cells to TP4. Our results showed that hedgehog was activated by TP4 in both WT and EGFR-mutant NSCLC cells and that pharmacological inhibition of hedgehog by vismodegib, a Food and Drug Administration-approved hedgehog inhibitor, potentiated TP4-induced cytotoxicity. Mechanistically, vismodegib acted by enhancing TP4-mediated increases in mitochondrial membrane potential and intracellular reactive oxygen species (ROS). MitoTempo, a specific mitochondrial ROS scavenger, abolished vismodegib/TP4 cytotoxicity. The combination of vismodegib with TP4 also reduced the levels of the antioxidant proteins catalase and superoxide dismutase, and it diminished the levels of chemoresistance-related proteins, Bcl-2 and p21. Thus, we conclude that hedgehog regulates the cytotoxic sensitivity of NSCLC cells to TP4 by protecting against mitochondrial dysfunction and suppressing oxidative stress. These findings suggest that combined treatment of vismodegib and TP4 may be a promising therapeutic strategy for NSCLC.
Palabras clave
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: Probiotics Antimicrob Proteins Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
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: Probiotics Antimicrob Proteins Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos