Journal of experimental & clinical cancer research, 2019-11, Vol.38 (1), p.448-13, Article 448
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells
- Ist Teil von
- Journal of experimental & clinical cancer research, 2019-11, Vol.38 (1), p.448-13, Article 448
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2019
- Quelle
- SpringerLink
- Beschreibungen/Notizen
- A natural compound Jaspine B and its derivative possess potential anti-cancer activities; However, little is known about the underlying mechanism. Here, the role of a new autophagy inducer Jaspine B derivative C-2 in suppressing bladder cancer cells was researched in vitro and in vivo. The underlying mechanisms and anticancer effect of C-2 in bladder cancer cells were investigated by MTT, western blotting, immunoprecipitation and immunofluorescence assays. The key signaling components were investigated by using pharmacological inhibitors or specific siRNAs. In vivo, we designed a C-2 and SP600125 combination experiment to verify the effectiveness of compound. C-2 exhibits cytotoxic effect on bladder cancer cells, and JNK activated by C-2 triggers autophagy and up-regulates SQSTM1/p62 proteins, contributing to activation of Nrf2 pathway. Utilization of JNK inhibitor SP600125 or knockdown of JNK by siRNA potentiate the cytotoxicity of C-2 through down-regulation of p62 and LC3II proteins and up-regulation of active-Caspase3 proteins, enhance the cell death effect, facilitating the switch from autophagy to apoptosis. In vivo study, C-2 suppresses tumor growth in a xenograft mouse model of EJ cells without observed toxicity. Combined treatment with SP600125 further enhances tumor inhibition of C-2 associated with enhanced activation of caspase3 and reduction of autophagy. It reveals a series of molecular mechanisms about SP600125 potentiate the cytotoxicity and tumor inhibition of C-2 in bladder cancer cells through promoting C-2-induced apoptosis, expecting it provides research basis and theoretical support for new drugs development.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1756-9966, 0392-9078eISSN: 1756-9966DOI: 10.1186/s13046-019-1467-6Titel-ID: cdi_doaj_primary_oai_doaj_org_article_5ef981e02a1b43d29fecfa3e0195ba82
- Format
- –
- Schlagworte
- Analysis, Animals, Anthracenes - administration & dosage, Anthracenes - pharmacology, Apoptosis, Autophagy, Autophagy - drug effects, Biochemistry, Bladder cancer, C-2, Cancer, Cancer cells, Care and treatment, Caspase 3 - metabolism, Cell Line, Tumor, Cell Proliferation - drug effects, Cell Survival - drug effects, Drug Synergism, Humans, Investigations, MAP Kinase Kinase 4, Mice, Oncology, Experimental, Proteins, Sequestosome-1 Protein - metabolism, SP600125, Sphingosine - analogs & derivatives, SQSTM1/p62, Treatment Outcome, Urinary Bladder Neoplasms - drug therapy, Urinary Bladder Neoplasms - metabolism, Xenograft Model Antitumor Assays