ArticleInvestigational new drugs2010
Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification.
Article in Investigational new drugs, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Genistein - A Broad-spectrum Bioactive Compound with Diverse Pharmacological Potential: A Systematic Review.Current molecular medicine · 2026Pooled it
- Isoflavones as multi-target modulators in glioma and neuroblastoma: a mini-review.Pharmacological reports : PR · 2026Review
- Dietary Polyphenols as Natural Modulators of NF-κB Signaling in Inflammation-Driven Non-Communicable Diseases: Focus on Cancer.Food science & nutrition · 2026Review
- Genistein as a Chemo-modulatory Agent: Exploring its Potential in Chemosensitization and Combinatorial Therapeutic Strategies for Cancer Treatment.Current topics in medicinal chemistry · 2025Review
- Cymensifin A: a promising pharmaceutical candidate to defeat lung cancer via cellular reactive oxygen species-mediated apoptosis.Frontiers in pharmacology · 2024Article
- Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits.Oxidative medicine and cellular longevity · 2021Review
- STAT3 and p53: Dual Target for Cancer Therapy.Biomedicines · 2020Review
- Novasoy and genistein inhibit endometrial cancer cell proliferation through disruption of the AKT/mTOR and MAPK signaling pathways.American journal of translational research · 2018Article
- Antiangiogenic Effect of Flavonoids and Chalcones: An Update.International journal of molecular sciences · 2017Review
- Novel combination of sorafenib and biochanin-A synergistically enhances the anti-proliferative and pro-apoptotic effects on hepatocellular carcinoma cells.Scientific reports · 2016Article
- Cancer prevention and therapy through the modulation of the tumor microenvironment.Seminars in cancer biology · 2015Review
- Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/-3 expression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- A mechanism linking Id2-TGFβ crosstalk to reversible adaptive plasticity in neuroblastoma.PloS one · 2013Article
- Synergistic anti-cancer mechanisms of curcumin and paclitaxel for growth inhibition of human brain tumor stem cells and LN18 and U138MG cells.Neurochemistry international · 2012Article
- Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells.Clinics (Sao Paulo, Brazil) · 2012Article
- Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells.Investigational new drugs · 2012Article
- Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway.World journal of surgical oncology · 2012Article
- Management of neuroblastoma: a study of first- and second-line chemotherapy responses, a single institution experience.Oncology reviews · 2012Article
- Targeting angiogenesis for controlling neuroblastoma.Journal of oncology · 2012Article
- Valproic acid induced differentiation and potentiated efficacy of taxol and nanotaxol for controlling growth of human glioblastoma LN18 and T98G cells.Neurochemical research · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroblastoma is an extracranial, solid, and heterogeneous malignancy in children. The conventional therapeutic modalities are mostly ineffective and thus new therapeutic strategies for malignant neuroblastoma are urgently warranted. We examined the synergistic efficacy of combination of sorafenib (SF) and genistein (GST) in human malignant neuroblastoma SK-N-DZ (N-Myc amplified) and SH-SY5Y (N-Myc non-amplified) cell lines. MTT assay showed dose-dependent decrease in cell viability and the combination therapy more prominently inhibited the cell proliferation in both cell lines than either treatment alone. Apoptosis was confirmed morphologically by Wright staining. Flow cytometric analysis of cell cycle phase distribution and Annexin V-FITC/PI staining showed increase in subG1 DNA content and early apoptosis, respectively, after treatment with the combination of drugs. Apoptosis was further confirmed by scanning electron microscopy. Combination therapy showed activation of caspase-8, cleavage of Bid to tBid, increase in p53 and p21 expression, down regulation of anti-apoptotic Mcl-1, and increase in Bax:Bcl-2 ratio to trigger apoptosis. Down regulation of MDR, hTERT, N-Myc, VEGF, FGF-2, NF-κB, p-Akt, and c-IAP2 indicated suppression of angiogenic and survival pathways. Mitochondrial release of cytochrome c and Smac into cytosol indicated involvement of mitochondia in apoptosis. Increases in proteolytic activities of calpain and caspase-3 were also confirmed. Our results suggested that combination of SF and GST inhibited angiogenic and survival factors and increased apoptosis via receptor and mitochondria mediated pathways in both neuroblastoma SK-N-DZ and SH-SY5Y cell lines. Thus, this combination of drugs could be a potential therapeutic strategy against human malignant neuroblastoma cells having N-Myc amplification or non-amplification.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.