D'Onofrio 2020 Sci Rep

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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.

» PMID: 32488123 Open Access

D'Onofrio Nunzia, Cacciola Nunzio Antonio, Martino Elisa, Borrelli Francesca, Fiorino Ferdinando, Lombardi Assunta, Neglia Gianluca, Balestrieri Maria Luisa, Campanile Giuseppe (2020) Sci Rep

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