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Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2020 Mar; Vol. 24 (6), pp. 3359-3369. Date of Electronic Publication: 2020 Jan 28. - Publication Year :
- 2020
-
Abstract
- The purpose of the present study was to evaluate the anti-cancer property of Lobetyolin on colorectal cancer and explore its potential mechanism. Lobetyolin was incubated with HCT-116 cells in the absence or presence of ASCT2 inhibitor Benser or p53 inhibitor Pifithrin-α. The levels of glutamine, glutamic acid, α-ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V-FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT-qPCR, Western blot and immunofluorescence staining. The expressions of cleaved-caspase-3, caspase-3, cleaved-caspase-7, caspase-7, cleaved-PARP, PARP, p53, p21, bax and survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced apoptosis and glutamine metabolism in HCT-116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine-related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT-116 was related to the expressions of p21 and bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin-α promoted the inhibitory effect of Lobetyolin on ASCT2-mediated apoptosis. Lobetyolin also exerted anti-cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the apoptosis via the inhibition of ASCT2-mediated glutamine metabolism, which was possibly governed by p53.<br /> (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Benzothiazoles pharmacology
Cell Line, Tumor
Colonic Neoplasms pathology
HCT116 Cells
Humans
Mice
Mice, Nude
Minor Histocompatibility Antigens
Toluene analogs & derivatives
Toluene pharmacology
Amino Acid Transport System ASC antagonists & inhibitors
Antineoplastic Agents pharmacology
Apoptosis physiology
Colonic Neoplasms drug therapy
Glutamine metabolism
Polyynes pharmacology
Tumor Suppressor Protein p53 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31990147
- Full Text :
- https://doi.org/10.1111/jcmm.15009