The Synthetic Flavonoid Derivative GL-V9 Induces Apoptosis and Autophagy in Cutaneous Squamous Cell Carcinoma via Suppressing AKT-Regulated HK2 and mTOR Signals.
Molecules
; 25(21)2020 Oct 30.
Article
en En
| MEDLINE
| ID: mdl-33143000
ABSTRACT
Cutaneous squamous-cell carcinoma (cSCC) is one of most common type of non-black skin cancer. The malignancy degree and the death risk of cSCC patients are significantly higher than basal cell carcinoma patients. GL-V9 is a synthesized flavonoid derived from natural active ingredient wogonin and shows potent growth inhibitory effects in liver and breast cancer cells. In this study, we investigated the anti-cSCC effect and the underlying mechanism of GL-V9. The results showed that GL-V9 induced both apoptosis and autophagy in human cSCC cell line A431 cells, and prevented the growth progression of chemical induced primary skin cancer in mice. Metabolomics assay showed that GL-V9 potentially affected mitochondrial function, inhibiting glucose metabolism and Warburg effect. Further mechanism studies demonstrated that AKT played important roles in the anti-cSCC effect of GL-V9. On one hand, GL-V9 suppressed AKT-modulated mitochondrial localization of HK2 and promoted the protein degradation of HK2, resulting in cell apoptosis and glycolytic inhibition. On the other hand, GL-V9 induced autophagy via inhibiting Akt/mTOR pathway. Interestingly, though the autophagy induced by GL-V9 potentially antagonized its effect of apoptosis induction, the anti-cSCC effect of GL-V9 was not diluted. All above, our studies suggest that GL-V9 is a potent candidate for cSCC treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Autofagia
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Flavonoides
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Carcinoma de Células Escamosas
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Apoptosis
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China