Topological properties and in vitro identification of essential nodes of the Paclitaxel and Vincristine interactomes in PC-3 cells

作者: Claudia Delgado-Carreño , Gina Méndez-Callejas

DOI: 10.1016/J.BJ.2019.04.003

关键词:

摘要: Abstract Background Microtubule-targeting agents (MTAs) disrupt microtubule dynamics, thereby inducing apoptosis via mitochondrial pathway activation through the modulation in expression of Bcl-2 family. Methods To describe topological features MTAs networks associated to intrinsic induction p53-null prostate cancer cells, we predicted and compared interactomes properties Paclitaxel Vincristine, thus, essential nodes corresponding with pro- anti-apoptotic proteins their kinetics were subjected experimental analysis PC-3 cell line. Results The apoptotic pathways, TP53, CASP3, identified both, Vincristine networks, but markers BCL2, BAX, BCL2L1 as hub only network. An in vitro demonstrated an increase BimEL cleaved-caspase-3 PC-3 cells exposed both treatments. Immunoprecipitation showed that treatments induced releasing Bax from complex protein role a de-repressor sequestering complexes, addition, new complexes between or cleaved-caspase-3, contributing data network for cells response MTAs. Conclusion differences sensitivities, profiles, observed drugs confirmed selectivity stimulation system vary depending on cell's genotype, drug used its exposure period.

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