ORIGINAL ARTICLE   

Minerva Biotechnology and Biomolecular Research 2021 September;33(3):135-40

DOI: 10.23736/S2724-542X.20.02634-8

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

Diallyl disulfide regulates proliferation, apoptosis and aerobic glycolysis by down-regulating PKM2 in gastric cancer cells

Zhiyan LI ¹, Baiwei ZHAO ², Deyao ZHANG ², Juan DENG ¹, Yongming CHEN ² ✉, Jian ZHOU ³

¹ Department of Gastroenterology, Hunan Provincial People’s Hospital Xingsha Branch, Changsha, China; ² Department of Gastroenterology, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; ³ Department of Radiology, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China

BACKGROUND: The aim of this study was to identify the mechanisms by which diallyl disulfide (DADS) regulates proliferation, apoptosis and aerobic glycolysis by down-regulating PKM2 in gastric cancer cells.
METHODS: HGC-27 gastric cancer cells were cultured. The glucose concentration and lactate level in the medium were examined using a Glucose Colorimetric Assay Kit II and a Lactate Assay Kit, respectively. Cell lysates were analyzed by western blot using antibodies specific for PKM2, LDHA, Mcl-1, Bcl-XL and GAPDH, and the mRNA levels of PKM2 were determined by real-time PCR using specific primers. shRNA-PKM2 was transfected into HGC-27 cells using Lipofectamine 2000. Cellular growth inhibition was assayed using the CCK8 method. Statistical analyses were performed using SPSS 17.0 software.
RESULTS: Inhibition of anaerobic glycolysis was observed in diallyl disulfide-treated HGC-27 cells, including an increased glucose concentration in the medium, decreased lactate production in the medium and down-regulation of PKM2, LDHA, Mcl-1 and Bcl-xl expression. Furthermore, down-regulation of PKM2 inhibited proliferation and induced apoptosis in HGC-27 human gastric cancer cells in vitro and in vivo. We further found that DADS did not significantly suppress anaerobic glycolysis or proliferation and induced apoptosis when down-regulating PKM2.
CONCLUSIONS: DADS suppressed proliferation and induced apoptosis in HGC-27 human gastric cancer cells by suppressing aerobic glycolysis through the down-regulation of PKM2. These results indicated that PKM2 may serve as a potential gene therapy target.

KEY WORDS: Diallyl disulfide; Stomach neoplasms; Glycolysis