PMID- 30514289 OWN - NLM STAT- MEDLINE DCOM- 20190115 LR - 20211204 IS - 1472-6882 (Electronic) IS - 1472-6882 (Linking) VI - 18 IP - 1 DP - 2018 Dec 4 TI - Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells. PG - 317 LID - 10.1186/s12906-018-2380-9 [doi] LID - 317 AB - BACKGROUND: Autophagy occurs in cells that undergoing nutrient deprivation. Glycolysis rapidly supplies energy for the proliferation of cancer cells. Cardamonin inhibits proliferation and enhances autophagy by mTORC1 suppression in ovarian cancer cells. Here, we investigate the relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression. METHODS: Treated with indicated compounds, ATP content and the activity of hexokinase (HK) and lactate dehydrogenase (LDH) were analyzed by the assay kits. Autophagy was detected by monodansylcadaverin (MDC) staining. The relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression was analyzed by Western blot. RESULTS: We found that cardamonin inhibited the lactate secretion, ATP production, and the activity of HK and LDH. The results demonstrated that cardamonin enhanced autophagy in SKOV3 cells, as indicated by acidic compartments accumulation, microtubule-associated protein 1 Light Chain 3-II (LC3-II) and lysosome associated membrane protein 1 up-regulation. Our results showed that the activation of mTORC1 signaling and the expression HK2 were reduced by cardamonin; whereas the phosphorylation of AMPK (AMP-activated protein kinase) was increased. We also confirmed that the AMPK inhibitor, Compound C, reversed cardamonin-induced upregulation of LC3-II. CONCLUSION: These results suggest that cardamonin-induced autophagy is associated with inhibition on glycolysis by down-regulating the activity of mTORC1 in ovarian cancer cells. FAU - Shi, Daohua AU - Shi D AUID- ORCID: 0000-0002-3383-5640 AD - Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China. shidh@yeah.net. FAU - Zhao, Di AU - Zhao D AD - Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China. FAU - Niu, Peiguang AU - Niu P AD - Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China. FAU - Zhu, Yanting AU - Zhu Y AD - Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China. FAU - Zhou, Jintuo AU - Zhou J AD - Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China. FAU - Chen, Huajiao AU - Chen H AD - Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China. LA - eng GR - 2016J01492/Natural Science Foundation of Fujian Province/ GR - 2017J01234/Natural Science Foundation of Fujian Province/ GR - 2017-1-18/Youth Foundation of Fujian Provincial Health and Family Planning Commission/ GR - 2017-1-19/Youth Foundation of Fujian Provincial Health and Family Planning Commission/ GR - 2016-CX-13/Innovative Medical Foundation of Fujian Provincial Health and Family Planning Commission/ PT - Journal Article DEP - 20181204 PL - England TA - BMC Complement Altern Med JT - BMC complementary and alternative medicine JID - 101088661 RN - 0 (Chalcones) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - H8KP1OJ8JX (cardamonin) SB - IM MH - Autophagy/*drug effects MH - Cell Line, Tumor MH - Chalcones/*pharmacology MH - Glycolysis/*drug effects MH - Humans MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors/*metabolism PMC - PMC6278091 OTO - NOTNLM OT - AMPK OT - Autophagy OT - Cardamonin OT - Glycolysis OT - mTOR COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/12/06 06:00 MHDA- 2019/01/16 06:00 PMCR- 2018/12/04 CRDT- 2018/12/06 06:00 PHST- 2018/07/04 00:00 [received] PHST- 2018/11/20 00:00 [accepted] PHST- 2018/12/06 06:00 [entrez] PHST- 2018/12/06 06:00 [pubmed] PHST- 2019/01/16 06:00 [medline] PHST- 2018/12/04 00:00 [pmc-release] AID - 10.1186/s12906-018-2380-9 [pii] AID - 2380 [pii] AID - 10.1186/s12906-018-2380-9 [doi] PST - epublish SO - BMC Complement Altern Med. 2018 Dec 4;18(1):317. doi: 10.1186/s12906-018-2380-9.