American Association for Cancer Research
mct-22-0191_supplementary_materials__methods_suppsmm.docx (17.69 kB)

Supplementary Materials & Methods from Griseofulvin Radiosensitizes Non–Small Cell Lung Cancer Cells and Activates cGAS

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journal contribution
posted on 2023-04-03, 08:40 authored by Xing Wang, Natasha Raman, Ghali Lemtiri-Chlieh, Jinhee Chang, Shreya Jagtap, Dipanwita Dutta Chowdhury, Matthew Ballew, Francesca Anna Carrieri, Triet Nguyen, Katriana Nugent, Travis Peck, Michelle S. Levine, Aaron Chan, Christine Lam, Reem Malek, Tung Hoang, Ryan Phillips, ZhuoAn Cheng, Kekoa Taparra, Nick Connis, Christine L. Hann, Andrew Holland, Phuoc T. Tran, Audrey Lafargue, Hailun Wang

Supplementary Materials & Methods


National Cancer Institute (NCI)

United States Department of Health and Human Services

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Prostate Cancer Foundation (PCF)

U.S. Department of Defense (DOD)

Uniting Against Lung Cancer

Johns Hopkins and Allegheny Health

Anonymous donor

Radiological Society of North America (RSNA)



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.

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