ArticleWorld journal of gastroenterology2024
Thymoquinone affects hypoxia-inducible factor-1α expression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways.
Article in World journal of gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- A novel photosensitizer berberine derivative B12 induces apoptosis and suppresses HIF-1α expression in colorectal cancer cells via mitochondria-to-nucleus sequential-targeting.Acta pharmacologica Sinica · 2026Article
- Enhancing the Water Solubility and Efficacy of Anticancer Drugs Using Hydroxypropyl-β-Cyclodextrin.International journal of molecular sciences · 2026Review
- Article
- Hydroxypropyl‑β‑cyclodextrin/thymoquinone inclusion complex inhibits non‑small cell lung cancer progression through NF‑κB‑mediated ferroptosis.Oncology reports · 2025Article
- Heat Shock Proteins in Pancreatic Cancer: Pathogenic Mechanisms and Clinical Implications.Cells · 2025Review
- Potential role of thymoquinone to treat gastrointestinal cancers: insights into its molecular mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Structure-based discovery and experimental validation of HIT101481851 as a potential PKMYT1 inhibitor for pancreatic cancer.Frontiers in pharmacology · 2025Article
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Abstract
backgroundPancreatic cancer (PC) is associated with some of the worst prognoses of all major cancers. Thymoquinone (TQ) has a long history in traditional medical practice and is known for its anti-cancer, anti-inflammatory, anti-fibrosis and antioxidant pharmacological activities. Recent studies on hypoxia-inducible factor-1α (HIF-1α) and PC have shown that HIF-1α affects the occurrence and development of PC in many aspects. In addition, TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α. Therefore, we speculate whether TQ affects HIF-1α expression in PC cells and explore the mechanism.
aimTo elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1α expression.
methodsCell counting kit-8 assay, Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity, migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial (hTERT-HPNE) cells. Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1α mRNA and protein in PC cells. The effects of TQ on the HIF-1α protein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.
resultsTQ significantly inhibited proliferative activity, migration, and invasion ability and promoted apoptosis of PANC-1 cells; however, no significant effects on hTERT-HPNE cells were observed. TQ significantly reduced the mRNA and protein expression levels of HIF-1α in PANC-1, AsPC-1, and BxPC-3 cells. TQ significantly inhibited the expression of the HIF-1α initial expression pathway (PI3K/AKT/mTOR) related proteins, and promoted the ubiquitination degradation of the HIF-1α protein in PANC-1 cells. TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1α protein but affected the stability of the HIF-1α protein by inhibiting the interaction between HIF-1α and HSP90, thus promoting its ubiquitination degradation.
conclusionThe regulatory mechanism of TQ on HIF-1α protein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1α protein by inhibiting the interaction between HIF-1α and HSP90; Secondly, TQ reduced the initial expression of HIF-1α protein by inhibiting the PI3K/AKT/mTOR pathway.
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