Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism.
J Cell Mol Med
; 24(6): 3359-3369, 2020 03.
Article
in En
| MEDLINE
| ID: mdl-31990147
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Suppressor Protein p53
/
Apoptosis
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Colonic Neoplasms
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Amino Acid Transport System ASC
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Polyynes
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Glutamine
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Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
J Cell Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2020
Type:
Article
Affiliation country:
China