bafilomycin-a1 has been researched along with Sarcoma-180* in 2 studies
2 other study(ies) available for bafilomycin-a1 and Sarcoma-180
Article | Year |
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Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death.
Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structure-activity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 μM against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlich's ascitic and solid Sarcoma-180 mouse models. Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Cell Line, Tumor; Diterpenes; Drug Design; Female; Halogenation; Humans; Membrane Proteins; Mice; Proto-Oncogene Proteins c-bcl-2; Salvia; Sarcoma 180; Signal Transduction; TOR Serine-Threonine Kinases | 2015 |
Role of autophagy in sonodynamic therapy-induced cytotoxicity in S180 cells.
Few reports have been published on the potential role of autophagy in the efficacy of sonodynamic therapy (SDT). This study was to determine whether autophagy occurred after SDT and to investigate its relationship with apoptosis by performing inhibitor studies. In vitro murine sarcoma 180 (S180) cells were examined at different time points following SDT. Transmission electron microscopy (TEM) was used to identify the formation of autophagosomes. Western blots were used to assess the processing of LC3-I to LC3-II. Confocal microscopy was performed to reveal co-localization between mitochondria and autophagic vacuoles and re-distribution of apoptosis related proteins after sono-damage. Inhibitors of apoptosis and autophagy were used to determine the contributions of the two cellular responses to SDT efficacy. Autophagy was indentified by TEM observation of the presence of double-membrane delineated autophagic vesicles and by immunoblot observation of the increased LC3-II levels. The autophagy inhibitors, both 3-methyladenine (3-MA) and Bafilomycin A1 (Ba A1), were found to significantly enhance SDT-induced cell death. Blocking autophagy also led to increased dissipation of mitochondria potential, caspase-3 activity and the ultimate cell apoptosis. Whereas the pan-caspase inhibitor, z-VAD-fmk partially prevented SDT-induced cytotoxicity but did not obviously improve the autophagic vacuolization and mitochondria depolarization. This study suggests for the first time that autophagy participate in SDT-induced cell death and combination of SDT with autophagy inhibitors, especially preventing autophagy at the early stage by 3-MA, can significantly enhance the anti-tumor effect of SDT through induction of apoptosis and necrosis. Topics: Adenine; Analysis of Variance; Animals; Apoptosis; Autophagy; Blotting, Western; Caspase 3; Cell Line, Tumor; Macrolides; Mice; Microscopy, Confocal; Sarcoma 180; Staining and Labeling; Ultrasonic Therapy | 2010 |