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  • ROS-Mediated Apoptotic Cell Death of Human Colon Cancer LoVo Cells by Milk δ-Valerobetaine.

ROS-Mediated Apoptotic Cell Death of Human Colon Cancer LoVo Cells by Milk δ-Valerobetaine.

Scientific reports (2020-06-04)
Nunzia D'Onofrio, Nunzio Antonio Cacciola, Elisa Martino, Francesca Borrelli, Ferdinando Fiorino, Assunta Lombardi, Gianluca Neglia, Maria Luisa Balestrieri, Giuseppe Campanile
要旨

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.

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製品内容

Sigma-Aldrich
N-アセチル-L-システイン, Sigma Grade, ≥99% (TLC), powder
Sigma-Aldrich
チアゾリルブルーテトラゾリウムブロミド, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
2',7'-ジクロロフルオレセイン二酢酸, ≥97%
Sigma-Aldrich
クロロキン 二リン酸塩, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
メナジオン, crystalline
Sigma-Aldrich
アミロイドタンパク質非Aβ成分, ≥80% (HPLC)