Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

作者: Mariela Rivera , Yanilda Ramos , Madeline Rodríguez-Valentín , Sheila López-Acevedo , Luis A. Cubano

DOI: 10.1371/JOURNAL.PONE.0179587

关键词: Programmed cell deathSignal transductionDownregulation and upregulationCurcuminCancer researchCalreticulinCancer cellBiologyUnfolded protein responseMolecular biologyApoptosis

摘要: Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, detailed mechanism underlying its pro-apoptotic anti-cancer effects remains be elucidated. In present study, we examined signaling pathways triggered by curcumin, specifically, exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cells. The effect was evaluated using for first time cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at gene expression level qRT-PCR protein western blot flow cytometry. Our findings revealed induced Endoplasmic Reticulum stress-mediated PC3. which promoted death these cells associated cycle arrest, increased reactive oxygen species, autophagy Unfolded Protein Response. Furthermore, upregulation ER stress measured key indicators stress: Glucose-Regulated 78, Inositol-Requiring Enzyme 1 alpha, Disulfide isomerase Calreticulin. Chronic induction concomitant markers (caspases 3,9,12) Poly (ADP-ribose) polymerase. downregulated proteins include anti-apoptotic anti-tumor markers, supporting their role Taken together, suggest serve as promising anticancer agent inducing chronic mediated activation UPR, oxidative responses.

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