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Griseofulvin Radiosensitizes Non-Small Cell Lung Cancer Cells and Activates cGAS.
Wang, Xing; Raman, Natasha; Lemtiri-Chlieh, Ghali; Chang, Jinhee; Jagtap, Shreya; Chowdhury, Dipanwita Dutta; Ballew, Matthew; Carrieri, Francesca Anna; Nguyen, Triet; Nugent, Katriana; Peck, Travis; Levine, Michelle S; Chan, Aaron; Lam, Christine; Malek, Reem; Hoang, Tung; Phillips, Ryan; Cheng, ZhuoAn; Taparra, Kekoa; Connis, Nick; Hann, Christine L; Holland, Andrew; Tran, Phuoc T; Lafargue, Audrey; Wang, Hailun.
Afiliação
  • Wang X; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Raman N; Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
  • Lemtiri-Chlieh G; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Chang J; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Jagtap S; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Chowdhury DD; Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland.
  • Ballew M; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Carrieri FA; Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland.
  • Nguyen T; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Nugent K; Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland.
  • Peck T; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Levine MS; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Chan A; Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland.
  • Lam C; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Malek R; Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland.
  • Hoang T; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Phillips R; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Cheng Z; Department of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Taparra K; Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland.
  • Connis N; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Hann CL; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Holland A; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Tran PT; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
  • Lafargue A; Department of Radiation Oncology, The Mayo Clinic, Rochester, Minnesota.
  • Wang H; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
Mol Cancer Ther ; 22(4): 519-528, 2023 04 03.
Article em En | MEDLINE | ID: mdl-36752776
Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non-small cell lung cancer (NSCLC). Griseofulvin (GF; FDA-approved treatment) inhibits CC, and combined with radiation treatment (RT), resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiation treatment resulted in a significant tumor growth delay. Both GF and radiation treatment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radioresistant cells that was dependent on cGAS. In conclusion, GF increased radiation treatment efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiation treatment, and immunotherapy could be a promising strategy to treat NSCLC.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article