Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppression of the constitutively active STAT3 with a concomitant increase in expression of protein tyrosine phosphatase (SHP-1). SNG treatment of MM cells leads to down-regulation of the anti-apoptotic proteins including cyclin D, Bcl-2, Bclxl, and XIAP. In addition, it also upregulates pro-apoptotic protein, Bax. SNG mediated cellular DNA damage in MM cell lines by induction of oxidative stress through the generation of reactive oxygen species and depletion of glutathione. Finally, the subtoxic concentration of SNG enhanced the cytotoxic effects of anticancer drugs bortezomib (BTZ) by suppressing the viability of MM cells via induction of caspase-mediated apoptosis. Altogether our findings demonstrate that SNG induces mitochondrial and caspase-dependent apoptosis, generates oxidative stress, and suppresses MM cell lines proliferation. In addition, co-treatment of...
Publication date: Available online 30 May 2020Source: Redox BiologyAuthor(s): Desong Kong, Zili Zhang, Liping Chen, Weifang Huang, Feng Zhang, Ling Wang, Yu Wang, Peng Cao, Shizhong Zheng
Publication date: Available online 30 May 2020Source: Life SciencesAuthor(s): Qi Fu, Zhenhai Yu
Publication date: Available online 29 May 2020Source: Life SciencesAuthor(s): Xiaoping Pan, Chen Wang, Yan Li, Lida Zhu, Ti Zhang
Publication date: Available online 29 May 2020Source: Life SciencesAuthor(s): Nagesh Kishan Panchal, E.P. Sabina
Publication date: Available online 29 May 2020Source: Carbohydrate PolymersAuthor(s): Juntao Tang, Yang Li, Yang Song, Xinyun Wu, Guipeng Yu, Kam Chiu Tam
In this study, five machine learning algorithms and twelve types of molecular fingerprints were employed to generate QSAR discriminant models for mitochondrial toxicity. A threshold moving method was adopted to resolve the imbalance issue in the training data. Consensus of the models by an averaging probability strategy improved prediction performance. The best model has correct classification rates of 81.8% and 88.3% in ten-fold cross validation and external validation, respectively. Substructures such as phenol, carboxylic acid, nitro and arylchloride were found informative through analysis of information gain and freque...
Publication date: Available online 29 May 2020Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Changyong Guo, Qirong Wang, Xingjie Zhang, Fengkun Lu, Miao Sun, Peiyu Zeng, Linhong Sun, Lan She, Bingkai Wang, Yunchang Zhang, Chen Wang, Zhiqiang Ma, Feng Yang
Publication date: Available online 29 May 2020Source: Journal of Electroanalytical ChemistryAuthor(s): Masaki Motoike, Keisuke Kimura, Yuki Kitazumi, Kenji Kano, Osamu Shirai
Donald Trump and Mike Pence witness launch in FloridaFirst attempt was cancelled minutes from blast-offA rocketship named Dragon breathed new fire into America ’s human spaceflight programme on Saturday, carrying two astronauts on a much-anticipated adventure.Related:Trump wants America looking at the stars as he drags it through the gutterContinue reading...
Publication date: Available online 30 May 2020Source: Urology Case ReportsAuthor(s): Andrew Moe, Isaac Thyer, Rajalingam Sinniah, Dickon Hayne
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