Format

Send to

Choose Destination
BMC Complement Altern Med. 2018 Dec 4;18(1):317. doi: 10.1186/s12906-018-2380-9.

Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells.

Author information

1
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.
2
Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China.

Abstract

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.

KEYWORDS:

AMPK; Autophagy; Cardamonin; Glycolysis; mTOR

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center