P53 regulates mitochondrial biogenesis via transcriptionally induction of mitochondrial ribosomal protein L12

Han, Yang‐Su; Liu, Yi; Zhen, Junhui; Hou, Shaoshuai; Zhang, Bo; Cui, ZhengGuo; Wan, Qiang; Hong, Feng

doi:10.1016/j.yexcr.2022.113249

Cited by 6 publications

(2 citation statements)

References 48 publications

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“…For assessing the release of mitochondrial DNA (mtDNA) into the cytosol, qRT-PCR analysis was carried out with primers specific for D-Loop2 and G6PC to evaluate mtDNA and nuclear DNA (nDNA), respectively. The copy number of mtDNA was determined by estimating the ratio mtDNA/nDNA . The primer sequences are listed in Table .…”

Section: Methodsmentioning

confidence: 99%

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A Novel Inhibitor of Poly(ADP-Ribose) Polymerase-1 Inhibits Proliferation of a BRCA-Deficient Breast Cancer Cell Line via the DNA Damage–Activated cGAS–STING Pathway

Jin,

Wang,

Jin

et al. 2024

Chem. Res. Toxicol.

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Loss-of-function mutations in the Breast Cancer Susceptibility Gene (BRCA1 and BRCA2) are often detected in patients with breast cancer. Poly(ADP-ribose) polymerase-1 (PARP1) plays a key role in the repair of DNA strand breaks, and PARP inhibitors have been shown to induce highly selective killing of BRCA1/2-deficient tumor cells, a mechanism termed synthetic lethality. In our previous study, a novel PARP1 inhibitor(E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)-N-(4-fluorophenyl) hydrazine-1-carbothioamide (4F-DDC)was synthesized, which significantly inhibited PARP1 activity with an IC50 value of 82 ± 9 nM. The current study aimed to explore the mechanism(s) underlying the antitumor activity of 4F-DDC under in vivo and in vitro conditions. 4F-DDC was found to selectively inhibit the proliferation of BRCA mutant cells, with highly potent effects on HCC-1937 (BRCA1–/–) cells. Furthermore, 4F-DDC was found to induce apoptosis and G2/M cell cycle arrest in HCC-1937 cells. Interestingly, immunofluorescence and Western blot results showed that 4F-DDC induced DNA double strand breaks and further activated the cGAS–STING pathway in HCC-1937 cells. In vivo analysis results revealed that 4F-DDC inhibited the growth of HCC-1937-derived tumor xenografts, possibly via the induction of DNA damage and activation of the cGAS–STING pathway. In summary, the current study provides a new perspective on the antitumor mechanism of PARP inhibitors and showcases the therapeutic potential of 4F-DDC in the treatment of breast cancer.

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Section: Methodsmentioning

confidence: 99%

“…The copy number of mtDNA was determined by estimating the ratio mtDNA/nDNA. 17 The primer sequences are listed in Table 1. 2.9.…”

Section: 7mentioning

confidence: 99%