Accumulating evidence has witnessed the Kelch-like ECH-associated protein 1(KEAP1)- nuclear factor (erythroid-derived 2)-like 2 (Nrf2) axis is the main regulatory factor of cell resistance to endogenous and exogenous oxidative assaults. However, there are few studies addressing the upstream regulatory factors of KEAP1. Herein, bioinformatic analysis suggests bromodomain-containing protein 4 (BRD4) as a potential top transcriptional regulator of KEAP1 in lung cancer. Using molecular and pharmacological approaches, we then discovered that BRD4 can directly bind to the promoter of to activate its transcription and down-regulate the stability of Nrf2 which in turn transcriptionally suppresses glucose-6-phosphate dehydrogenase (G6PD) in small cell lung cancer (SCLC), a highly proliferative and aggressive disease with limited treatment options. In addition, BRD4 could associate with the Nrf2 protein in a non-KEAP1-dependent manner to inhibit Nrf2 activity. Furthermore, simultaneous application of JQ1 and ATRA or RRx-001 yielded synergistic inhibition both in vitro and in vivo. These data suggest metabolic reprogramming by JQ1 treatment improves cell resistance to oxidative stress and might be a resistance mechanism to bromodomain and extra-terminal domain (BET) inhibition therapy. Altogether, our findings provide novel insight into the transcriptional regulatory network of BRD4 and KEAP1 and transcriptional regulation of the pentose phosphate pathway in SCLC.
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http://dx.doi.org/10.3390/antiox11040661 | DOI Listing |
Nat Prod Res
January 2025
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.
Powdered germinated Thai rice () is widely utilised as a dietary supplement to support health and prevent diseases. This study investigated the bioactive compound profile of water extracts from beverage powder made from Thai germinated brown rice (GBRE) and assessed its anticancer effects on cholangiocarcinoma, lung cancer, and liver cancer cell lines. Proton nuclear magnetic resonance (1H-NMR) revealed 23 metabolites, including amino acids, sugar, phenolic compounds and nitrogenous compounds.
View Article and Find Full Text PDFCancer Med
February 2025
Pulmonology and Thoracic Oncology Department, APHP Hôpital Tenon and Sorbonne Université, Paris, France.
Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.
Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).
Pharmaceutics
January 2025
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
In the original publication [...
View Article and Find Full Text PDFPharmaceutics
January 2025
Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, China.
: (PG) has been widely researched as a conductant drug for the treatment of lung diseases by ancient and modern traditional Chinese medicine (TCM) practitioners. Inspired by the mechanism and our previous finding about fructans and fructooligosaccharides from (FFPG), we developed a nano drug delivery system (NDDS) targeting lung cancer. The aim was to improve the efficiency of the liposomal delivery of Paclitaxel (PTX) and enhance the anti-tumor efficacy.
View Article and Find Full Text PDFPharmaceutics
January 2025
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8573, Ibaraki, Japan.
Orally administered sorafenib has shown limited improvement in overall survival for non-small-cell lung cancer patients, likely due to poor pharmacokinetics and adverse effects, including gastrointestinal toxicity. To address these issues, we developed silica-containing antioxidant nanoparticles (siRNP) as a carrier to enhance the therapeutic efficacy of lipophilic sorafenib. Sorafenib was loaded into siRNP via dialysis (sora@siRNP).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!