ArticleWorld journal of gastroenterology2015
β-elemene enhances the radiosensitivity of gastric cancer cells by inhibiting Pak1 activation.
Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Recent advances in lycopene and germacrene a biosynthesis and their role as antineoplastic drugs.World journal of microbiology & biotechnology · 2024Review
- β-Elemene promotes ferroptosis and reverses radioresistance in gastric cancer by inhibiting the OTUB1-GPX4 interaction.Frontiers in pharmacology · 2024Article
- Assessment of the Oxidative Damage and Genotoxicity of Titanium Dioxide Nanoparticles and Exploring the Protective Role of Holy Basil Oil Nanoemulsions in Rats.Biological trace element research · 2023Article
- Circular RNA hsa_circ_0004396 acts as a sponge of miR-615-5p to promote non-small cell lung cancer progression and radioresistance through the upregulation of P21-Activated Kinase 1.Journal of clinical laboratory analysis · 2022Article
- Blockage of PAK1 alleviates the proliferation and invasion of NSCLC cells via inhibiting ERK and AKT signaling activity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Anti-Tumor Drug Discovery Based on Natural Product β-Elemene: Anti-Tumor Mechanisms and Structural Modification.Molecules (Basel, Switzerland) · 2021Review
- miR-144-3p increases radiosensibility of gastric cancer cells by targeting inhibition of ZEB1.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- PAK1 silencing is synthetic lethal with CDK4/6 inhibition in gastric cancer cells via regulating PDK1 expression.Human cell · 2020Article
- The Antitumor Efficacy ofBioMed research international · 2020Review
- The Use of ß-Elemene to Enhance Radio Sensitization of A375 Human Melanoma Cells.Cell journal · 2020Article
- β‑elemene inhibits the generation of peritoneum effusion in pancreatic cancer via suppression of the HIF1A‑VEGFA pathway based on network pharmacology.Oncology reports · 2019Article
- Beta-elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation.Journal of cellular and molecular medicine · 2019Article
- β-elemene inhibits radiation and hypoxia-induced macrophages infiltration via Prx-1/NF-κB/HIF-1α signaling pathway.OncoTargets and therapy · 2019Article
- Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.Chinese medicine · 2019Review
- B7-H3 increases the radioresistance of gastric cancer cells through regulating baseline levels of cell autophagy.American journal of translational research · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms.
methodsSGC7901, MKN45, MKN28, N87, and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death, respectively. A proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation (IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1 (Pak1) to target Pak1 signaling. Protein levels of PAK1IP1 (p21-activated protein kinase-interacting protein 1), total Pak1 (t-Pak1), phospho-Pak1 (T423), phospho-ERK1/2 (Thr202/Tyr204), and cleaved caspase-3 (17 kDa) were assessed by western blotting.
resultsMKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally, β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45 (10.4% ± 0.9% vs 34.8% ± 2.8%, P < 0.05) and SGC7901 (11.6% ± 0.9% vs 46.7% ± 5.2%, P < 0.05) human gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Through iTRAQ analysis and western blot validation, we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1 (T423) and phospho-ERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1 (T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition, IPA-3 increased radiation-induced cell death in MKN45 (13.4% ± 0.3% vs 26.6% ± 1.0%, P < 0.05) and SGC7901 (16.0% ± 0.6% vs 37.3% ± 1.7%, P < 0.05) gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation.
conclusionThis is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells, and that the mechanism involves inhibition of Pak1 signaling.
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