ArticleInternational journal of oncology2015
Combination treatment with triptolide and hydroxycamptothecin synergistically enhances apoptosis in A549 lung adenocarcinoma cells through PP2A-regulated ERK, p38 MAPKs and Akt signaling pathways.
Article in International journal of oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Triptolide: A Narrative Review of Its Traditional Use, Derivatives, Pharmacology, Antitumor Effect, and Clinical Applications.Cancers · 2026Review
- Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- CUL4B mutations impair human cortical neurogenesis through PP2A-dependent inhibition of AKT and ERK.Cell death & disease · 2024Article
- Development of 10-Hydroxycamptothecin-crizotinib conjugate based on the synergistic effect on lung cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Targeting the RNA-Binding Protein HuR in Cancer.Cancer research · 2023Review
- Neddylation inhibitor MLN4924 sensitizes head and neck squamous carcinoma cells to (S)-10-hydroxycamptothecin.European journal of medical research · 2023Article
- Dual Drug-Loaded Nanoliposomes Encapsulating Curcumin and 5-Fluorouracil with Advanced Medicinal Applications: Self-Monitoring and Antitumor Therapy.Molecules (Basel, Switzerland) · 2023Article
- Therapeutic Effects of Synthetic Triblock Amphiphilic Short Antimicrobial Peptides on Human Lung Adenocarcinoma.Pharmaceutics · 2022Article
- Delivery of triptolide: a combination of traditional Chinese medicine and nanomedicine.Journal of nanobiotechnology · 2022Review
- Synergic effect of anticancer peptide CIGB-552 and Cisplatin in lung cancer models.Molecular biology reports · 2022Article
- Is Nucleoredoxin a Master Regulator of Cellular Redox Homeostasis? Its Implication in Different Pathologies.Antioxidants (Basel, Switzerland) · 2022Review
- PP2A promotes apoptosis and facilitates docetaxel sensitivity via the PP2A/p-eIF4B/XIAP signaling pathway in prostate cancer.Oncology letters · 2022Article
- A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non-Small Cell Lung Cancer.Frontiers in pharmacology · 2022Review
- Bi-Functional Peptides as a New Therapeutic Tool for Hepatocellular Carcinoma.Pharmaceutics · 2021Article
- ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer.Cells · 2021Review
- Perspectives and controversies regarding the use of natural products for the treatment of lung cancer.Cancer medicine · 2021Review
- Triptolide-induced apoptosis in non-small cell lung cancer via a novel miR204-5p/Caveolin-1/Akt-mediated pathway.Oncotarget · 2020Article
- Triptolide interrupts rRNA synthesis and induces the RPL23‑MDM2‑p53 pathway to repress lung cancer cells.Oncology reports · 2020Article
- Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells.Oncology reports · 2020Article
- 2-phenylethynesulfonamide inhibits growth of oral squamous cell carcinoma cells by blocking the function of heat shock protein 70.Bioscience reports · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is the leading cause of cancer death worldwide. Recently, two plant-derived drugs triptolide (TP) and hydroxycamptothecin (HCPT) both have shown broad-spectrum anticancer activities. Our previous study documented that combination treatment with these two drugs acted more effectively than mono-therapy, however, the molecular basis underlying the synergistic cytotoxicity remains poorly understood. In this study, we aimed to clarify the molecular mechanism of TP/HCPT anticancer effect in A549 lung adenocarcinoma cells, by investigating the involvement of phosphatase 2A (PP2A) and PP2A-regulated mitogen-activated protein kinases (MAPKs) and Akt signaling pathways. The results showed that TP and HCPT synergistically exerted cytotoxicity in the growth of A549 cells. Combinatorial TP/HCPT treatment significantly enhanced the activation of caspase-3 and -9, Bax/Bcl-2 ratio, release of cytochrome c from mitochondrial and subsequent apoptosis. While the Akt survival pathway was inhibited, ERK and p38 MAPKs were dramatically activated. Furthermore, the activity of PP2A was significantly augmented. Regulation of p38, ERK and Akt by PP2A was demonstrated, by using a specific PP2A inhibitor okadaic acid (OA). Finally, pharmacological inhibitors OA, SB203580, SP600125 and PD98059 confirm the role of PP2A and its substrates ERK, p38 MAPK and Akt in mediating TP/HCPT-induced apoptosis. Taken together, this study provides the first evidence for a synergistic TP/HCPT anticancer activity in A549 cells and also supports a critical role of PP2A and PP2A-regulated signaling pathways, providing new insight into the mode of action of TP/HCPT in cancer therapy.
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