ArticleScientific reports2018
Silibinin, A Natural Blend In Polytherapy Formulation For Targeting Cd44v6 Expressing Colon Cancer Stem Cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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16 citing papers in PubMed, 40 citations in OpenAlex.
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- Endophytic fungi: A future prospect for breast cancer therapeutics and drug development.Heliyon · 2024Review
- Role of CD44 isoforms in epithelial-mesenchymal plasticity and metastasis.Clinical & experimental metastasis · 2022Review
- Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells.Marine drugs · 2022Article
- Inhibition and potential treatment of colorectal cancer by natural compoundsFrontiers in oncology · 2022Review
- Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Advances in Liver Cancer Stem Cell Isolation and their Characterization.Stem cell reviews and reports · 2021Review
- Sterenin M as a potential inhibitor of SARS-CoV-2 main protease identified from MeFSAT database using molecular docking, molecular dynamics simulation and binding free energy calculation.Computers in biology and medicine · 2021Article
- Molecular insight into isoform specific inhibition of PI3K-α and PKC-η with dietary agents through an ensemble pharmacophore and docking studies.Scientific reports · 2021Article
- PANC-1 cancer stem-like cell death with silybin encapsulated in polymersomes and deregulation of stemness-related miRNAs and their potential targets.Iranian journal of basic medical sciences · 2021Article
- Functional analysis of CD44 variants and xCT in canine tumours.Veterinary medicine and science · 2021Article
- Endophytic fungi: A treasure trove of novel anticancer compounds.Current research in pharmacology and drug discovery · 2021Article
- Transcriptome profiling reveals Silibinin dose-dependent response network in non-small lung cancer cells.PeerJ · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colon cancer stem cells have been attributed to poor prognosis, therapeutic resistance and aggressive nature of the malignancy. Recent reports associated CD44v6 expression with relapse, metastasis and reduced 5-year survival of colon cancer patients, thereby making it a potential therapeutic target. Thus, in this study, comprehensive prediction and screening of CD44v6 against 1674 lead compounds was conducted. Silibinin was identified as a potential compound targeting CD44v6. Inorder to substantiate these findings, the cytotoxic effect of 5FU, Silibinin and 5FU+ Silibinin was assessed on human colon carcinoma cell line HCT116 derived CD44+ subpopulation. 5FU+ Silibinin inhibited cell proliferation of CD44+ subpopulation at lower concentration than Silibinin standalone. Further, corresponding to CD44v6 knockdown cells, 5FU+ Silibinin treatment significantly decreased CD44v6, Nanog, CTNNB1 and CDKN2A expression whereas increased E-cadherin expression in HCT116 derived CD44+ cells. Moreover, synergistic effect of these drugs suppressed sphere formation, inhibited cell migration, triggered PARP cleavage and perturbation in mitochondrial membrane potential, thereby activating intrinsic apoptotic pathways and induced autophagic cell death. Importantly, 5FU+ Silibinin could inhibit PI3K/MAPK dual activation and arrest the cell cycle at G0/G1 phase. Thus, our study suggests that inhibition of CD44v6 attenuates stemness of colon cancer stem cells and holds a prospect of potent therapeutic target.
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