Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 22;8(1):133.
doi: 10.1038/s41392-023-01326-6.

Promotion of liquid-to-solid phase transition of cGAS by Baicalein suppresses lung tumorigenesis

Tiansheng Zheng #  1   2 , Haipeng Liu #  3 , Yifan Hong #  4   5 , Yajuan Cao  3 , Qing Xia  1   2   4 , Chengge Qin  4   6 , Ming Li  2   4 , Russel J Reiter  7 , Yidong Bai  7 , Lihong Fan  8   9   10
Affiliations

Promotion of liquid-to-solid phase transition of cGAS by Baicalein suppresses lung tumorigenesis

Tiansheng Zheng et al. Signal Transduct Target Ther. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Baicalein promotes the liquid-to-solid phase transition of cGAS to suppress lung tumorigenesis. a Hematoxylin and eosin (H&E) staining of the section of lung tissue from mice of indicated groups. A lung adenocarcinoma (LUAD) model using conditional alleles of KrasLSL-G12D; p53flox/flox in mice (KP mice) was established. The mice were divided into three groups, one group was treated with adenovirus expressing Cre recombinase and fed with a normal diet (Cre), and the other group was also treated with adenovirus expressing Cre recombinase and mixed with Baicalein in a normal diet (Cre+Baicalein). The third group was treated with control adenovirus and fed with a normal diet (Cre) (Blank). Scale bars left: 200 μm. The red frame indicates the magnified area, which is shown on the right side. b The analysis of the number of tumors formed in one lobe of the left lung in mice of the indicated groups. The symbol indicates one mouse from n = 6 mice per group. The data shown are representative of n = 3 independent experiments. Data were expressed as the mean ± SD and one-way ANOVA followed by Dunnett’s post hoc test was used for the statistical analysis. c Gene set enrichment analysis (GSEA) for oxidative phosphorylation pathways correlated with the differentially expressed genes (DEGs). d Heatmap of DEGs in the pathway of cytosolic DNA-sensing. e qRT-PCR measurement of mtDNA in MEF cells treated as indicated. DNA was extracted from digitonin extracts of MEF cells generated from LSL-KrasG12D/WT;p53flox/flox mice that has been stably transduced with HBAD-Cre (Cre) left untreated or treated with Baicalein (60 μM) for 24 h. Cytosolic mtDNA was quantitated via qRT-PCR using a mitochondrial D-loop primer set. Normalization was performed as described in the Methods. f Oxygen consumption rate (OCR) in untreated MEF cells (Control) or MEF cells that has been stably transduced with an empty vector (Vehicle) or HBAD-Cre (Cre) in the absence of the presence of Baicalein (60 μM) for 24 h. n = 3. g, h Representative confocal microscopy images showing the presence of dsDNA in MEF cells that has been stably transduced with HBAD-Cre (Cre) in the absence of the presence of Baicalein (60 μM) for 24 h. Cells were stained with MitoTracker Red (red), Picogreen (green), and DAPI (blue), visualized by confocal microscopy. Scale bars = 10 μm. The quantification of the cytosolic Picogreen signal is shown in (d). i qRT-PCR measurement of Ifnb1 transcripts in the lung of mice as in (Fig. 1a). j–l qRT-PCR measurement of transcripts of Ifnb1 (a), Cxcl10 (b), and Ccl5 (c) in untreated MEF cells generated from LSL-KrasG12D/WT;p53flox/flox mice (Blank), and MEF cells that has been stably transduced with an empty vector (Vehicle) or an HBAD-Cre (Cre) in the absence or presence of Baicalein at indicated concentrations for 12 h. n = 3. m Immunoblotting of indicated protein in untreated MEF cells generated from LSL-KrasG12D/WT;p53flox/flox mice (Blank), and MEF cells that has been stably transduced with an empty vector (Vehicle) or an HBAD-Cre (Cre) in the absence or presence of Baicalein at indicated concentrations for 12 h. n Surface Plasmon Resonance (SPR) assay showing the binding of Baicalein with cGAS (Kd = 3.02 μM). o An ELISA assay of the production of cGAMP by purified SUMO-cGAS in the absence or presence of ISD left untreated or treated with increasing dose of Baicalein. p FRAP assay of mEGFP-cGAS in Hela cells. The intensity was normalized with the pre-bleached as 100%. Graphical data were mean ± SD. Statistical analyses were done using unpaired Student’s t-test (d, f) or one-way ANOVA followed by Dunnett’s post hoc test (a). *p < 0.05; **p < 0.01
See this image and copyright information in PMC

References

    1. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553:446–454. doi: 10.1038/nature25183. - DOI - PubMed
    1. Kamp WM, Wang PY, Hwang PM. TP53 mutation, mitochondria and cancer. Curr. Opin. Genet. Dev. 2016;38:16–22. doi: 10.1016/j.gde.2016.02.007. - DOI - PMC - PubMed
    1. DuPage M, Dooley AL, Jacks T. Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nat. Protoc. 2009;4:1064–1072. doi: 10.1038/nprot.2009.95. - DOI - PMC - PubMed
    1. de Oliveira MR, et al. The effects of baicalein and baicalin on mitochondrial function and dynamics: a review. Pharm. Res. 2015;100:296–308. doi: 10.1016/j.phrs.2015.08.021. - DOI - PubMed
    1. Zhang L, et al. Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review. J. Exp. Clin. Cancer Res. 2022;41:227. doi: 10.1186/s13046-022-02439-6. - DOI - PMC - PubMed

Publication types