ArticleMolecular biology reports2020
The synergistic anti-proliferative effect of the combination of diosmin and BEZ-235 (dactolisib) on the HCT-116 colorectal cancer cell line occurs through inhibition of the PI3K/Akt/mTOR/NF-κB axis.
Article in Molecular biology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Synergistic Targeting of Hepatocellular Carcinoma via Novel Regorafenib Combinations with Diosmin, Sulfasalazine, or Rosuvastatin.Biochemical genetics · 2026Article
- Identification of a Novel Peptide fromFoods (Basel, Switzerland) · 2025Article
- Identification of diabetes-related signatures as prognostic and therapeutic biomarkers in colon cancer.Discover oncology · 2025Article
- Diosmin induces mitochondrial-mediated apoptosis and anti-inflammatory effects in Hep-2 cells: an integrated in vitro and in silico analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Repurposing of sericin combined with dactolisib or vitamin D to combat non-small lung cancer cells through computational and biological investigations.Scientific reports · 2024Article
- Diosmin ameliorates inflammation, apoptosis and activates PI3K/AKT pathway in Alzheimer's disease rats.Metabolic brain disease · 2024Article
- Diosmin: A promising phytochemical for functional foods, nutraceuticals and cancer therapy.Food science & nutrition · 2024Review
- High glucose inhibits autophagy and promotes the proliferation and metastasis of colorectal cancer through the PI3K/AKT/mTOR pathway.Cancer medicine · 2024Article
- Total Flavonoids inInternational journal of molecular sciences · 2023Article
- Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells.Probiotics and antimicrobial proteins · 2023Article
- Nanomedicine for cancer targeted therapy with autophagy regulation.Frontiers in immunology · 2023Review
- Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines.Contemporary oncology (Poznan, Poland) · 2023Article
- Quercetin potentiates 5-fluorouracil effects in human colon cancer cells through targeting the Wnt/β-catenin signalling pathway: the role of miR-27a.Contemporary oncology (Poznan, Poland) · 2022Article
- Effect of Regorafenib on P2X7 Receptor Expression and Different Oncogenic Signaling Pathways in a Human Breast Cancer Cell Line: A Potential of New Insight of the Antitumor Effects of Regorafenib.Current issues in molecular biology · 2021Article
- Catalpol synergistically potentiates the anti-tumour effects of regorafenib against hepatocellular carcinoma via dual inhibition of PI3K/Akt/mTOR/NF-κB and VEGF/VEGFR2 signaling pathways.Molecular biology reports · 2021Article
- Combinatorial antitumor effects of amino acids and epigenetic modulations in hepatocellular carcinoma cell lines.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?International journal of molecular sciences · 2021Review
- Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer.Translational oncology · 2021Review
- Article
- Combating TKI resistance in CML by inhibiting the PI3K/Akt/mTOR pathway in combination with TKIs: a review.Medical oncology (Northwood, London, England) · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the most lethal malignancies worldwide is colorectal cancer (CRC). Alterations in various signalling pathways, including PI3K-mTOR and NF-κB, have been reported in CRC with subsequent dysregulation of proliferation, apoptosis, angiogenesis and, questionably, autophagy processes. BEZ-235 (dactolisib) is a dual PI3K-mTOR inhibitor with potent anti-tumour activity. However, the observed toxicity of BEZ-235 necessitated the termination of its clinical trials. Hence, we aimed to evaluate the potential long-lasting anti-carcinogenic effects of adding diosmin (DIO, a natural NF-κB inhibitor) to BEZ-235 in HCT-116 CRC cells. The median inhibitory concentrations (IC50s) of BEZ-235 and/or DIO were evaluated in the HCT-116 CRC cell line. Caspase-3 activity was assessed colorimetrically, and p-Akt, NF-κB, CD1, VEGF and LC3B levels were assessed by ELISA. Additionally, LC3-II and P62 gene expression were assessed using qRT-PCR. The observed CIs (combination indices) and DRIs (dose reduction indices) confirmed the synergistic effect of DIO and BEZ-235. Co-administration of both drugs either in combination-1 (1 μM for BEZ-235, 250 μM for DIO) or in combination-2 (0.51 μM for BEZ-235 + 101.99 μM for DIO) inhibited the PI3K/Akt/mTOR/NF-κB axis, leading to the induction of apoptosis (via active caspase-3), and the inhibition of proliferation marker (CD1), angiogenesis marker (VEGF), autophagy protein (LC3B) and altered effects on LC3-IIandP62 gene expression. Our results reveal the synergistic chemotherapeutic effects of DIO combined with BEZ-235 in the HCT-116 CRC cell line and encourage future preclinical and clinical studies of this combination with reduced BEZ-235 concentrations to avoid its reported toxicity.
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