ArticleInternational journal of oncology2016
Chemosensitizing effect of podophyllotoxin acetate on topoisomerase inhibitors leads to synergistic enhancement of lung cancer cell apoptosis.
Article in International journal of oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles.Frontiers in pharmacology · 2022Pooled it
- Diversity of oxidative stress and senescence phenotypes induced by chemotherapeutic agents in HUVECs.Scientific reports · 2025Article
- Reversal of the tamoxifen‑resistant breast cancer malignant phenotype by proliferation inhibition with bromosulfonamidine amino‑podophyllotoxin.Oncology letters · 2024Article
- Neddylation inhibitor MLN4924 sensitizes head and neck squamous carcinoma cells to (S)-10-hydroxycamptothecin.European journal of medical research · 2023Article
- Chemistry and Biological Activities of Naturally Occurring and Structurally Modified Podophyllotoxins.Molecules (Basel, Switzerland) · 2022Review
- JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs.Frontiers in cell and developmental biology · 2021Review
- Gimatecan exerts potent antitumor activity against gastric cancer in vitro and in vivo via AKT and MAPK signaling pathways.Journal of translational medicine · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Podophyllotoxin acetate (PA) acts as a radiosensitizer against non-small cell lung cancer (NSCLC) in vitro and in vivo. In this study, we examined its potential role as a chemosensitizer in conjunction with the topoisomerase inhibitors etoposide (Eto) and camptothecin (Cpt). The effects of combinations of PA and Eto/Cpt were examined with CompuSyn software in two NSCLC cell lines, A549 and NCI-H1299. Combination index (CI) values indicated synergistic effects of PA and the topoisomerase inhibitors. The intracellular mechanism underlying synergism was further determined using propidium iodide uptake, immunoblotting and electrophoretic mobility shift assay (EMSA). Combination of PA with Eto/Cpt promoted disruption of the dynamics of actin filaments, leading to subsequent enhancement of apoptotic cell death via induction of caspase-3, -8, and -9, accompanied by increased phosphorylation of p38. Conversely, suppression of p38 phosphorylation blocked the apoptotic effect of the drug combinations. Notably, CREB-1, a transcription factor, was constitutively activated in both cell types, and synergistically inhibited upon combination treatment. Our results collectively indicate that PA functions as a chemosensitizer by enhancing apoptosis through activation of the p38/caspase axis and suppression of CREB-1.
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