ArticleBMC cancer2021
Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Pooled it
- Regulatory Roles of Kaempferol on the PI3K/AKT/mTOR Signaling Pathway and Associated MicroRNAs in Different Cancer Types.International journal of molecular sciences · 2026Review
- Interaction of NDRG1 and TGM2 Modulates DNA Replication and Repair.Molecular cancer research : MCR · 2026Article
- Exploring the Health Effects of Phytoestrogens.Metabolites · 2026Review
- Kaempferol as an ovarian aging-modulatory flavonol.Biogerontology · 2026Review
- Identification of prognostic genes and development of a risk model for pancreatic cancer based on hypoxia- and lipid metabolism-related genes.Discover oncology · 2026Article
- Hyaluronic acid/kaempferol-functionalized Fe₃O₄ nanoparticles promote ROS-associated apoptosis and modulate caspase-8/BCRT1 axis in triple-negative breast cancer.Scientific reports · 2026Article
- Inhibition of proliferation and metastasis of nasopharyngeal carcinoma by kaempferol via down-regulation of c-Jun.Translational cancer research · 2026Article
- Recent Progress on Polyphenols of Malaysian Honey and Their Molecular Mechanism Pathways in Cancer-A Comprehensive Review.International journal of molecular sciences · 2026Review
- Pigmented Sorghum Phenolic Extracts Regulate the Expression of Cancer Development Pathway Genes in HT-29 and Hypoxia-Induced CCD 841 CoN Cells.Food science & nutrition · 2026Article
- Kaempferol Inhibits MMP-1-Mediated Migration and Invasion in Gemcitabine-Resistant Pancreatic Cancer Cells.Nutrients · 2026Article
- Synergistic anticancer effect of ellagic acid and Kaempferol combination in a mouse model of breast cancer.Frontiers in oncology · 2026Article
- Targeting neuroimmune interactions: the therapeutic potential of kaempferol in immune-related central nervous system disorders.Frontiers in immunology · 2026Review
- Dose-dependent tuning of HSP70-Beclin-1 by kaempferol governs autophagy and chemosensitivity.Frontiers in oncology · 2026Article
- Leveraging the molecular insights and therapeutic potential of diet-derived-flavonoids against pancreatic ductal adenocarcinoma.Frontiers in pharmacology · 2026Review
- Acalypha australis L. induces autophagic cell death in colorectal cancer cells by increasing ROS through suppression of the AKT/mTOR/HIF-1 pathway.Frontiers in oncology · 2026Article
- TGM2-P2RX7 loop promotes gemcitabine resistance in pancreatic cancer by modulating glutamine metabolism and mitophagy.Cell death discovery · 2025Article
- Mitochondrial superoxide dismutase controls metabolic plasticity in pancreatic cancer.Cell communication and signaling : CCS · 2025Article
- Recent advances in hydrogel-based delivery systems for the treatment of pancreatic cancer.Materials today. Bio · 2025Review
- Mesenchymal stem cells-derived exosomes and Kaempferol improve myelin repair via attenuating inflammation and oxidative stress in a cuprizone-induced demyelination model.Stem cell research & therapy · 2025Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKaempferol, a natural flavonoid, exhibits anticancer properties by scavenging reactive oxygen species (ROS). However, increasing evidence has demonstrated that, under certain conditions, kaempferol can inhibit tumor growth by upregulating ROS levels. In this study, we aimed to investigate whether kaempferol effectively suppresses pancreatic cancer through upregulation of ROS, and to explore the underlying molecular mechanism.
methodsPANC-1 and Mia PaCa-2 cells were exposed to different concentrations of kaempferol. Cell proliferation and colony formation were evaluated by CCK-8 and colony formation assays. Flow cytometry was performed to assess the ROS levels and cell apoptosis. The mRNA sequencing and KEGG enrichment analysis were performed to identify differentially expressed genes and to reveal significantly enriched signaling pathways in response to kaempferol treatment. Based on biological analysis, we hypothesized that tissue transglutaminase (TGM2) gene was an essential target for kaempferol to induce ROS-related apoptosis in pancreatic cancer. TGM2 was overexpressed by lentivirus vector to verify the effect of TGM2 on the ROS-associated apoptotic signaling pathway. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. The prognostic value of TGM2 was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tools based on public data from the TCGA database.
resultsKaempferol effectively suppressed pancreatic cancer in vitro and in vivo. Kaempferol promoted apoptosis in vitro by increasing ROS generation, which was involved in Akt/mTOR signaling. TGM2 levels were significantly increased in PDAC tissues compared with normal tissues, and high TGM2 expression was positively correlated with poor prognosis in pancreatic cancer patients. Decreased TGM2 mRNA and protein levels were observed in the cells after treatment with kaempferol. Additionally, TGM2 overexpression downregulated ROS production and inhibited the abovementioned apoptotic signaling pathway.
conclusionsKaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling, and TGM2 may represent a promising prognostic biomarker for pancreatic cancer.
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Registered trials
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