D'Onofrio 2020 Sci Rep
|D'Onofrio N, Cacciola NA, Martino E, Borrelli F, Fiorino F, Lombardi A, Neglia G, Balestrieri ML, Campanile G (2020) ROS-mediated apoptotic cell death of human colon cancer LoVo cells by milk δ-valerobetaine. Sci Rep 10:8978.|
Abstract: δ-Valerobetaine (δVB) is a constitutive milk metabolite with antioxidant and anti-inflammatory activities. Here, we tested the antineoplastic properties of milk δVB on human colorectal cancer cells. CCD 841 CoN (non-tumorigenic), HT-29 (p53 mutant adenocarcinoma) and LoVo (APC/RAS mutant adenocarcinoma) cells were exposed to 3 kDa milk extract, δVB (2 mM) or milk+δVB up to 72 h. Results showed a time- and dose-dependent capability of δVB to inhibit cancer cell viability, with higher potency in LoVo cells. Treatment with milk+δVB arrested cell cycle in G2/M and SubG1 phases by upregulating p21, cyclin A, cyclin B1 and p53 protein expressions. Noteworthy, δVB also increased necrosis (P < 0.01) and when used in combination with milk it improved its activity on live cell reduction (P < 0.05) and necrosis (P < 0.05). δVB-enriched milk activated caspase 3, caspase 9, Bax/Bcl-2 apoptotic pathway and reactive oxygen species (ROS) production, whereas no effects on ROS generation were observed in CCD 841 CoN cells. The altered redox homeostasis induced by milk+δVB was accompanied by upregulation of sirtuin 6 (SIRT6). SIRT6 silencing by small interfering RNA blocked autophagy and apoptosis activated by milk+δVB, unveiling the role of this sirtuin in the ROS-mediated apoptotic LoVo cell death.
• Bioblast editor: Plangger M
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Cancer
Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Intact cells
Regulation: Cyt c
Pathway: CIV HRR: Oxygraph-2k