PMID- 32517736 OWN - NLM STAT- MEDLINE DCOM- 20210204 LR - 20211204 IS - 1756-9966 (Electronic) IS - 0392-9078 (Print) IS - 0392-9078 (Linking) VI - 39 IP - 1 DP - 2020 Jun 9 TI - 2,6-DMBQ is a novel mTOR inhibitor that reduces gastric cancer growth in vitro and in vivo. PG - 107 LID - 10.1186/s13046-020-01608-9 [doi] LID - 107 AB - BACKGROUND: Fermented wheat germ extract has been reported to exert various pharmacological activities, including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated. METHODS: Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis. Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed using gastric cancer patient-derived xenograft models. RESULTS: 2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived xenograft gastric tumor growth in an in vivo mouse model. CONCLUSIONS: 2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic implications for gastric cancer patients. FAU - Zu, Xueyin AU - Zu X AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. FAU - Ma, Xiaoli AU - Ma X AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. FAU - Xie, Xiaomeng AU - Xie X AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. FAU - Lu, Bingbing AU - Lu B AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. FAU - Laster, Kyle AU - Laster K AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. FAU - Liu, Kangdong AU - Liu K AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. AD - The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, Henan, China. AD - The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China. FAU - Dong, Zigang AU - Dong Z AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org. AD - The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org. AD - The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org. AD - International joint research center of cancer chemoprevention, Zhengzhou, China. zgdong@hci-cn.org. FAU - Kim, Dong Joon AU - Kim DJ AD - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. djkim@hci-cn.org. AD - China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. djkim@hci-cn.org. AD - The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China. djkim@hci-cn.org. LA - eng GR - U1804196/Henan Joint Fund/ GR - 81572812/National Natural Science Foundation China/ GR - 161100510300/Key program of Henan Province, China/ PT - Journal Article DEP - 20200609 PL - England TA - J Exp Clin Cancer Res JT - Journal of experimental & clinical cancer research : CR JID - 8308647 RN - 0 (Benzoquinones) RN - 0 (Biomarkers, Tumor) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - HET5TF8ZGO (2,6-dimethyl-1,4-benzoquinone) SB - IM MH - Animals MH - Apoptosis MH - Benzoquinones/*pharmacology MH - Biomarkers, Tumor MH - Cell Cycle MH - Cell Proliferation MH - Female MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - In Vitro Techniques MH - Mice MH - Mice, Nude MH - Prognosis MH - Protein Kinase Inhibitors/*pharmacology MH - Stomach Neoplasms/*drug therapy/metabolism/pathology MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors MH - Tumor Cells, Cultured MH - Xenograft Model Antitumor Assays PMC - PMC7285595 OTO - NOTNLM OT - 2,6-DMBQ OT - Gastric cancer OT - Patient-derived xenograft OT - mTOR OT - p70S6K COIS- None of the authors have any competing interests. EDAT- 2020/06/11 06:00 MHDA- 2021/02/05 06:00 PMCR- 2020/06/09 CRDT- 2020/06/11 06:00 PHST- 2020/02/22 00:00 [received] PHST- 2020/05/28 00:00 [accepted] PHST- 2020/06/11 06:00 [entrez] PHST- 2020/06/11 06:00 [pubmed] PHST- 2021/02/05 06:00 [medline] PHST- 2020/06/09 00:00 [pmc-release] AID - 10.1186/s13046-020-01608-9 [pii] AID - 1608 [pii] AID - 10.1186/s13046-020-01608-9 [doi] PST - epublish SO - J Exp Clin Cancer Res. 2020 Jun 9;39(1):107. doi: 10.1186/s13046-020-01608-9.