ArticleNutrients2023
Natural Flavonoids Quercetin and Kaempferol Targeting G2/M Cell Cycle-Related Genes and Synergize with Smac Mimetic LCL-161 to Induce Necroptosis in Cholangiocarcinoma Cells.
Article in Nutrients, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Molecular Mechanisms of the Anticancer Activity of the Flavonoid Kaempferol: A Comprehensive Review.Journal of cancer prevention · 2026Review
- Review
- Flavonoids as Dual Topoisomerase I and II Inhibitors: Mechanistic Insights and Emerging Anticancer Strategies.Chemistry & biodiversity · 2026Review
- Review
- Review
- Integrated analysis reveals survival-related genes promoting cholangiocarcinoma progression via G2/M cell cycle, with validation of cyclin B1 in tumor proliferation.Scientific reports · 2025Article
- Necroptosis-driven T cell activation promotes IL-6-mediated PD-L1 upregulation in cholangiocarcinoma cells: IL-6 gene signature as a biomarker for chemo-immunotherapy response.Biology direct · 2025Article
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- CDK4/6 inhibitors upregulate cIAP1/2, and Smac mimetic LCL161 enhances their antitumor effects in cholangiocarcinoma cells.Scientific reports · 2025Article
- Cytotoxicity, Proapoptotic Activity and Drug-like Potential of Quercetin and Kaempferol in Glioblastoma Cells: Preclinical Insights.International journal of molecular sciences · 2024Article
- Anti-Inflammatory and Cancer-Preventive Potential of Chamomile (Biomedicines · 2024Article
- Review
- Article
- Identification of Candidate Hub Genes and Drug Targets for Cholangiocarcinoma via Juhua (Chrysanthemum Morifolium) Bioactivity and Molecular Docking: A Bioinformatics Approach.Cancer management and research · 2024Article
- Targeting programmed cell death via active ingredients from natural plants: a promising approach to cancer therapy.Frontiers in pharmacology · 2024Review
- Antioxidant Activity of Quercetin-Containing Liposomes-in-Gel and Its Effect on Prevention and Treatment of Cutaneous Eczema.Pharmaceuticals (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cholangiocarcinoma (CCA) is an aggressive cancer associated with a very poor prognosis and low survival rates, primarily due to late-stage diagnosis and low response rates to conventional chemotherapy. Therefore, there is an urgent need to identify effective therapeutic strategies that can improve patient outcomes. Flavonoids, such as quercetin and kaempferol, are naturally occurring compounds that have attracted significant attention for their potential in cancer therapy by targeting multiple genes. In this study, we employed network pharmacology and bioinformatic analysis to identify potential targets of quercetin and kaempferol. The results revealed that the target genes of these flavonoids were enriched in G2/M-related genes, and higher expression of G2/M signature genes was significantly associated with shorter survival in CCA patients. Furthermore, in vitro experiments using CCA cells demonstrated that quercetin or kaempferol induced cell-cycle arrest in the G2/M phase. Additionally, when combined with a Smac mimetic LCL-161, an IAP antagonist, quercetin or kaempferol synergistically induced RIPK1/RIPK3/MLKL-mediated necroptosis in CCA cells while sparing non-tumor cholangiocyte cells. These findings shed light on an innovative therapeutic combination of flavonoids, particularly quercetin and kaempferol, with Smac mimetics, suggesting great promise as a necroptosis-based approach for treating CCA and potentially other types of cancer.
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