PloS one, 2013-10, Vol.8 (10), p.e77411
2013
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- Autor(en) / Beteiligte
- Titel
- Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo
- Ist Teil von
- PloS one, 2013-10, Vol.8 (10), p.e77411
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear. Cell viability was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections. Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA, APAF-1) was estimated by qRTPCR. Effect of Minnelide on proliferative cells in the tissue was estimated by Ki-67 staining of animal tissue sections. In this study, we investigated in vitro and in vivo antitumor effects of triptolide/Minnelide in non-small cell lung carcinoma (NSCLC). Triptolide/Minnelide exhibited anti-proliferative effects and induced apoptosis in NSCLC cell lines and NSCLC mouse models. Triptolide/Minnelide significantly down-regulated the expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulated pro-apoptotic APAF-1 gene, in part, via attenuating the NF-κB signaling activity. In conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0077411Titel-ID: cdi_plos_journals_1442193111
- Format
- –
- Schlagworte
- Analysis, Animal models, Animal tissues, Animals, Anticancer properties, Antineoplastic Agents - pharmacology, Antitumor activity, APAF-1 gene, Apaf-1 protein, Apoptosis, Apoptosis - drug effects, Cancer, Cancer therapies, Cancer treatment, Carcinoma, Carcinoma, Non-Small-Cell Lung - pathology, Care and treatment, Caspase, Cell Line, Tumor, Cell proliferation, Cell Proliferation - drug effects, Cell survival, Cell Survival - drug effects, Chemotherapy, Cholecystokinin, Cytotoxicity, Diterpenes, Gene expression, Genes, Health aspects, Heat shock proteins, Hsp70 protein, In vivo methods and tests, Kinases, Lung cancer, Lung cancer, Non-small cell, Lung carcinoma, Lung diseases, Lung Neoplasms - pathology, Medical prognosis, Mice, NF-kappa B - metabolism, NF-κB protein, Non-small cell lung cancer, Non-small cell lung carcinoma, Organophosphates - pharmacology, Phenanthrenes - pharmacology, Phosphorylation, Proteins, Signal Transduction - drug effects, Small cell lung carcinoma, Staining, Substrates, Surgery, Survival, Transcription factors, Transcription, Genetic - drug effects, Transcriptional Activation - drug effects, Triptolide, Tumor necrosis factor-TNF, Up-Regulation - drug effects, Xenograft Model Antitumor Assays