ArticleMolecular pharmacology2009
Etoposide induces protein kinase Cdelta- and caspase-3-dependent apoptosis in neuroblastoma cancer cells.
Article in Molecular pharmacology, 2009. 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, 37 citations in OpenAlex.
- Preferential enhancement of mitochondria-mediated apoptosis and modulation of metastasis-related markers by etoposide-loaded nanoparticles in breast cancer cell lines.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A novel prenylflavonoid with efficacy in cancer therapy by targeting ceramide-orchestrated signaling.Frontiers in pharmacology · 2026Article
- Cytotoxic and apoptotic effects of etoposide and ellagic acid alone or with possible synergistic/additive combinations on a canine D-17 osteosarcoma cell line.Veterinarni medicina · 2025Article
- Article
- An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.International journal of molecular sciences · 2024Review
- Necroptosis andFrontiers in microbiology · 2019Article
- Grb7 and Hax1 may colocalize partially to mitochondria in EGF-treated SKBR3 cells and their interaction can affect Caspase3 cleavage of Hax1.Journal of molecular recognition : JMR · 2016Article
- Temporal Heterogeneity Metrics in Apoptosis Induced by Anticancer Drugs.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2015Article
- Study on the cytotoxic activity of drimane sesquiterpenes and nordrimane compounds against cancer cell lines.Molecules (Basel, Switzerland) · 2014Article
- High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells.Phytotherapy research : PTR · 2014Article
- Synthesis of a new ent-cyclozonarone angular analog, and comparison of its cytotoxicity and apoptotic effects with ent-cyclozonarone.Molecules (Basel, Switzerland) · 2013Article
- Diterpenylhydroquinones from natural ent-labdanes induce apoptosis through decreased mitochondrial membrane potential.Molecules (Basel, Switzerland) · 2013Article
- Disruption of microRNA biogenesis confers resistance to ER stress-induced cell death upstream of the mitochondrion.PloS one · 2013Article
- Anti-proliferative effects of tricyclodecan-9-yl-xanthogenate (D609) involve ceramide and cell cycle inhibition.Molecular neurobiology · 2012Article
- An investigation into the cytotoxic effects of 13-acetoxysarcocrassolide from the soft coral Sarcophyton crassocaule on bladder cancer cells.Marine drugs · 2011Article
- Mechanism of pyrethroid pesticide-induced apoptosis: role of calpain and the ER stress pathway.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
- Induction of apoptosis in human promyelocytic leukemia HL60 cells by panaxynol and panaxydol.Molecules (Basel, Switzerland) · 2011Article
- Targeting gastrin-releasing peptide as a new approach to treat aggressive refractory neuroblastomas.Surgery · 2011Article
- Article
- Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway.World journal of gastroenterology · 2010Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In this report, we reveal that etoposide inhibits the proliferation of SK-N-AS neuroblastoma cancer cells and promotes protein kinase Cdelta (PKCdelta)- and caspase-dependent apoptosis. Etoposide induces the caspase-3-dependent cleavage of PKCdelta to its active p40 fragment, and active PKCdelta triggers the processing of caspase-3 by a positive-feedback mechanism. Treatment of cells with the caspase-3-specific inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone or caspase-3-specific small interacting RNA (siRNA) prevented the etoposide-induced activation of caspase-8 and inhibited apoptosis. The silencing of the caspase-2 or caspase-8 genes using siRNAs did not affect the etoposide-induced processing of caspase-3, indicating that these caspases lie downstream of caspase-3 in this signaling pathway. Furthermore, the etoposide-induced processing of caspase-2 required the expression of caspase-8, and the etoposide-mediated processing of caspase-8 required the expression of caspase-2, indicating that these two caspases activate each other after etoposide treatment. We also observed that etoposide-mediated apoptosis was decreased by treating the cells with the caspase-6-specific inhibitor benzyloxycarbonyl-Val-Glu(OMe)-Ile-Asp-(OMe)-fluoromethyl ketone and that caspase-6 was activated by a caspase-8-dependent mechanism. Finally, we show that rottlerin blocks etoposide-induced apoptosis by inhibiting the PKCdelta-mediated activation of caspase-3 and by degrading caspase-2, which prevents caspase-8 activation. Our results add important insights into how etoposide mediates apoptotic signaling and how targeting these pathways may lead to the development of novel therapeutics for the treatment of neuroblastomas.
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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.