In silico identification of potential protein kinase C alpha inhibitors from phytochemicals from IMPPAT database for anticancer therapeutics: a virtual screening approach

Article

作者: Almoyad, Mohammad Ali Abdullah ; Alshehri, Saad Ali ; Wahab, Shadma

Protein Kinase C alpha (PKCα) is a critical signaling molecule that plays a crucial role in various physiological processes, including cell growth, differentiation, and survival. Over the years, there has been a growing interest in targeting PKCα as a promising drug target for the treatment of various diseases, including cancer. Targeting PKCα can, therefore, serve as a potential strategy to prevent cancer progression and enhance the efficacy of conventional anticancer therapies. We conducted a systematic search for promising compounds for their anticancer potential that target PKCα using natural compounds from the IMPPAT database. The initial compounds were screened through various tests, including analysis of their physical and chemical properties, PAINS filter, ADMET analysis, PASS analysis, and specific interaction analysis. We selected those that showed high binding affinity and specificity to PKCα from the screened compounds, and we further analyzed them using molecular dynamics simulations (MDS) and principal component analysis (PCA). Various systematic parameters from the MDS analyses suggested that the protein-ligand complexes were stabilized throughout the simulation trajectories of 100 nanoseconds (ns). Our findings indicated that compounds Nicandrenone and Withaphysalin D bind to PKCα with high stability and affinity, making them potential candidates for further research in cancer therapeutics innovation in clinical contexts.Communicated by Ramaswamy H. Sarma.

2018-04-01·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research3区 · 生物学

In vitro identification of mitochondrial oxidative stress production by time-resolved fluorescence imaging of glioma cells

3区 · 生物学

Article

作者: Misuth, Matus ; Tomkova, Silvia ; Huntosova, Veronika ; Lenkavska, Lenka ; Miskovsky, Pavol

Oxidative phosphorylation and glycolysis are important features, by which cells could bypass oxidative stress. The level of oxidative stress, and the ability of cells to promote oxidative phosphorylation or glycolysis, significantly determined proliferation or cell demise. In the present work, we have employed selective mitochondrial probe MitoTracker™ Orange CMTM/Ros (MTO) to estimate the level of oxidative stress in cancer cells at different stressed conditions. MTO is partially sensitive to decrease of mitochondrial membrane potential and to reactive oxygen species (ROS) generated in mitochondria. We have demonstrated, that fluorescence lifetime of MTO is much more sensitive to oxidative stress than intensity-based approaches. This method was validated in different cancer cell lines. Our approach revealed, at relatively low ROS levels, that Gö 6976, a protein kinase C (PKC) α inhibitor, and rottlerin, an indirect PKCδ inhibitor, increased mitochondrial ROS level in glioma cell. Their involvement in oxidative phosphorylation and apoptosis was investigated with oxygen consumption rate estimation, western blot and flow-cytometric analysis. Our study brings new insight to identify feeble differences in ROS production in living cells.

2017-04-01·Journal of Ayurveda and Integrative Medicine

Involvement of tyrosine-specific protein kinase and protein kinase C in J774A.1 macrophage functions activated by Tinospora cordifolia

Article

作者: More, Priti ; Pai, Kalpana

BACKGROUNDMacrophages are the first line of defense and constitute important participant in the bi-directional interaction between innate and specific immunity. Macrophages are in a quiescent form and get activated when given a stimulus. In our previous studies we have reported that guduchi or LPS treatment of macrophages enhanced production of nitric oxide (NO) and increased tumoricidal activity against L929 fibroblast cells.OBJECTIVEIn the present study effect of Tinospora cordifolia commonly known as guduchi on macrophage activation and the mechanism of action i.e. involvement of protein kinase C inhibitor and tyrosine-specific protein kinase inhibitor was investigated.MATERIALS AND METHODSThe present study was undertaken to determine whether H-7 (inhibitor of protein kinase C) and/or genistein (inhibitor of tyrosine-specific protein kinase) could inhibit guduchi or LPS-induced macrophage NO and TNF-α production or reduce the cytolysis of L929 fibroblast cells.RESULTSIt was observed that in vitro incubation with H-7 and/or genistein completely inhibited guduchi or LPS-induced NO and TNF-α production by macrophages (J774A.1).CONCLUSIONThe inhibitory effects of H-7 and/or genistein, suggest that phosphorylation via these kinases may upregulate the NO synthase activity in macrophages.

100 项与 GAP-107B8 相关的药物交易

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