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ORIGINAL ARTICLE   

Minerva Biotecnologica 2020 September;32(3):114-20

DOI: 10.23736/S1120-4826.20.02617-8

Copyright © 2020 EDIZIONI MINERVA MEDICA

lingua: Inglese

Diallyl disulfide regulates energy metabolism by targeting AMP-activated protein kinase alpha1 in human gastric cancer cells

Xiaoyan ZHANG 1, Xueqi OU 2, Xiaoqing KUANG 1, Zhiyan LI 1, Nian FU 1, Jian ZHOU 2

1 Department of Gastroenterology, Nanhua Hospital, University of South China, Hengyang, China; 2 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiology, Sun Yat-sen University, Guangzhou, China



BACKGROUND: Diallyl disulfide (DADS), a sulfuric compound derived from garlic, exerts various biological effects such as anticancer, antiangiogenic and anti-inflammatory activities. However, the mechanisms of action underlying this compound’s anticancer activity have not been fully elucidated. The aim of this study was to identify the mechanism by which AMP-activated protein kinase alpha1 (AMPKα1) contributes to the anti-tumor effects of DADS.
METHODS: MGC-803 cells treated with 0, 10, 20, or 40 mg/L of DADS for 48 hours were examined for glucose and lactic acid concentrations, cell viability and apoptosis using colorimetric methods, a cell counting kit (CCK8) and flow cytometry, respectively. The protein expression levels of AMPKα1 and lactate dehydrogenase A (LDHA) in the cells were detected with western blotting. The mRNA expression of AMPKα1 was measured with quantitative real-time PCR (qRT-PCR), and shRNA targeting AMPKα1 as well as a scrambled shRNA were transfected into MGC-803 cells using Lipofectamine 2000.
RESULTS: Inhibition of aerobic glycolysis was observed in DADS-treated MGC-803 cells as indicated by increases in the glucose concentration in the medium, decreases of lactate production in the medium and down-regulation of AMPKα1 and LDHA expression. Meanwhile, DADS inhibited proliferation and induced apoptosis in a concentration-dependent manner. Furthermore, AMPKα1 was identified as a target of DADS. AMPKα1 is overexpressed in many cancers, and down-regulation of AMPKα1 inhibited proliferation and induced apoptosis of MGC-803 human gastric cancer cells in vitro by suppressing aerobic glycolysis induced by DADS.
CONCLUSIONS: We demonstrated that DADS could induce apoptosis, inhibit proliferation and suppress aerobic glycolysis by down-regulating AMPKα1.


KEY WORDS: Diallyl disulfide; Stomach neoplasms; Metabolism; Glycolysis

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