Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells

• DOI: 10.7717/peerj.2445
• Publication Date: 2016-11-15T08:45:38Z
• Authors: Ahmed A. Gafar; Hossam M. Draz; Alexander A. Gold...; Mohamed A. Bashandy; Sayed Bakry; Mahmoud A. Khalifa; Walid AbuShair; Vladimir I. Titor...; J. Thomas Sanderson
• Keywords: Lithocholic acid

Lithocholic acid (LCA) is a secondary bile that selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported LCA inhibited cell viability proliferation induced apoptosis necrosis of androgen-dependent LNCaP androgen-independent PC-3 In the present study, we investigated roles endoplasmic reticulum (ER) stress, autophagy mitochondrial dysfunction in toxicity deficient, DU-145 ER stress-related proteins, such as CCAAT-enhancer-binding protein homologous (CHOP), phosphorylation eukaryotic initiation factor 2-alpha (p-eIF2 α ) c-Jun N-terminal kinases (p-JNK) both cell-types. The p53 upregulated modulator (PUMA) B lymphoma-like 11 (BIM) levels were decreased at overtly concentrations, although PUMA increased lower concentrations lines. autophagy-related conversion microtubule-associated proteins 1A/1B light chain 3B (LC3BI–LC3BII), ATG5 but not autophagy-deficient (>10 µM) reactive oxygen species (ROS) concentration-dependently whereas ROS affected Salubrinal, an inhibitor eIF2 dephosphorylation reduced LCA-induced CHOP slightly PC-3, Salubrinal pre-treatment cytotoxicity cells resulted statistically significant loss normally non-toxic LCA. late-stage bafilomycin A1 exacerbated subtoxic antioxidant -tocotrienol strongly Collectively, induces stress these processes appear be initially protective nature subsequently consequential to, critical for ROS-mediated full mechanism similarly sensitive remains elucidated.