ArticleOncogene2003
PG490-mediated sensitization of lung cancer cells to Apo2L/TRAIL-induced apoptosis requires activation of ERK2.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 92 citations in OpenAlex.
- Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non-Small Cell Lung Cancer.Frontiers in pharmacology · 2022Review
- Improved Antitumor Outcomes for Colon Cancer Using Nanomicelles Loaded with the Novel Antitumor Agent LA67.International journal of nanomedicine · 2020Article
- The Roles of Plant-Derived Triptolide on Non-Small Cell Lung Cancer.Oncology research · 2019Review
- Pulmonary delivery of triptolide-loaded liposomes decorated with anti-carbonic anhydrase IX antibody for lung cancer therapy.Scientific reports · 2017Article
- Ethanolic extract of Descurainia sophia seeds sensitizes A549 human lung cancer cells to TRAIL cytotoxicity by upregulating death receptors.BMC complementary and alternative medicine · 2016Article
- Poncirus trifoliata Rafin. induces the apoptosis of triple-negative breast cancer cells via activation of the c-Jun NH(2)-terminal kinase and extracellular signal-regulated kinase pathways.Pharmacognosy magazine · 2015Article
- Mitochondrial inhibitor sensitizes non-small-cell lung carcinoma cells to TRAIL-induced apoptosis by reactive oxygen species and Bcl-X(L)/p53-mediated amplification mechanisms.Cell death & disease · 2014Article
- Selective tumor cell killing by triptolide in p53 wild-type and p53 mutant ovarian carcinomas.Medical oncology (Northwood, London, England) · 2014Article
- Mass cytometry to decipher the mechanism of nongenetic drug resistance in cancer.Current topics in microbiology and immunology · 2014Review
- Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo.PloS one · 2013Article
- Control of FLIP(L) expression and TRAIL resistance by the extracellular signal-regulated kinase1/2 pathway in breast epithelial cells.Cell death and differentiation · 2012Article
- Triptolide triggers the apoptosis of pancreatic cancer cells via the downregulation of Decoy receptor 3 expression.Journal of cancer research and clinical oncology · 2012Article
- Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5.International journal of oncology · 2012Article
- MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in a murine model of AML.Leukemia · 2012Article
- Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer.International journal of nanomedicine · 2012Article
- Triptolide and TRAIL combination enhances apoptosis in cholangiocarcinoma.The Journal of surgical research · 2010Article
- A new dawn for the use of traditional Chinese medicine in cancer therapy.Molecular cancer · 2009Review
- Article
- Conserved regulation of MAP kinase expression by PUF RNA-binding proteins.PLoS genetics · 2007Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) belongs to the family of programmed cell death-inducing cytokines. Apo2L/TRAIL induces apoptosis in a wide variety of tumor cells. Tumor cells that are resistant to Apo2L/TRAIL-induced apoptosis can be sensitized by chemotherapeutic drugs and other agents via an unknown mechanism. Here we report that PG490 (triptolide), a diterpene triepoxide extracted from the Chinese herb Tripterygium wilfordii and used in traditional Chinese medicine, sensitizes lung cancer but not normal human bronchial epithelial cells to Apo2L/TRAIL-induced apoptosis. Sensitization was accompanied by caspase-3 and caspase-8 activation, whereas no cleavage of caspase-9 was observed. Determination of cell surface receptors by flow cytometry demonstrated no difference in Apo2L/TRAIL-R1 and -R2 expression, the two receptors with functional death domains, between resistant and sensitized cells. In cells treated with the combination of Apo2L/TRAIL and PG490, we observed activation of ERK2, a member of the mitogen-activated protein kinase family. Furthermore, sensitization could be blocked by the ERK inhibitor U0126 but not the p38 inhibitor SB203580, suggesting that activation of ERK2 is required for this effect. In addition, sensitization of lung cancer cells was also seen in ex vivo culture of lung cancer tissue from four patients who underwent surgery. Immunohistochemical staining showed a clear reduction in proliferation cell nuclear antigen (PCNA) in tissue treated with Apo2L/TRAIL and PG490. In conclusion, apoptosis induced by the combination of Apo2L/TRAIL and PG490 warrants further evaluation as a potential new strategy for the treatment of lung cancer.
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