ArticleCellular oncology (Dordrecht, Netherlands)2018
Synergistic anticancer effect of panobinostat and topoisomerase inhibitors through ROS generation and intrinsic apoptotic pathway induction in cervical cancer cells.
Article in Cellular oncology (Dordrecht, Netherlands), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 45 citations in OpenAlex.
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- Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.Annals of medicine · 2023Review
- Panobinostat (LBH589) combined with AM1241 induces cervical cancer cell apoptosis through autophagy pathway.BMC pharmacology & toxicology · 2023Article
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- Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells.Frontiers in pharmacology · 2021Article
- An Overview of Novel Agents for Cervical Cancer Treatment by Inducing Apoptosis: Emerging Drugs Ongoing Clinical Trials and Preclinical Studies.Frontiers in medicine · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeVarious combinations of drugs may be effective in the treatment of different types of cancer. Previously, we have shown that combinations of the histone deacetylase inhibitor panobinostat and the topoisomerase inhibitors topotecan or etoposide act synergistically, but the underlying mode of action has remained unknown. Here, we aimed at uncovering the mechanisms underlying this synergism.
methodsThe effects of (combinations of) panobinostat and topotecan or etoposide on cervical cancer-derived HeLa and SiHa cells were assessed using morphological evaluations, scratch wound healing assays, cell cycle analyses, AO/EB staining assays, Annexin V/PI staining assays, reactive oxygen species (ROS) and mitochondrial membrane potential measurements and Western blotting.
resultsWe found that combinations of panobinostat and the topoisomerase inhibitors topotecan or etoposide synergistically enhanced the induction of apoptosis in both HeLa and SiHa cells. This enhanced apoptosis induction was found to be mediated through increased ROS production and induction of the mitochondrial apoptotic pathway. We also found that the combination treatment resulted in inhibition of the PI3K/AKT and NF-κB pro-survival pathways and in activation of the ERK pathway, which is associated with intrinsic apoptosis.
conclusionsFrom our data we conclude that combinations of panobinostat and the topoisomerase inhibitors topotecan or etoposide provoke strong cell death responses in cervical cancer-derived cells via induction of the intrinsic apoptotic pathway. Since this drug combination may potentially be effective in the treatment of cervical cancer, further preclinical investigations are warranted.
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