Antimalarial Dihydroartemisinin triggers autophagy within HeLa cells of human cervical cancer through Bcl-2 phosphorylation at Ser70.
Phytomedicine
; 52: 147-156, 2019 Jan.
Article
em En
| MEDLINE
| ID: mdl-30599894
ABSTRACT
BACKGROUND:
As an effective antimalarial medicine, Dihydroartemisinin (DHA) has therapeutic potential on human cervical cancer. However, its working mechanism has not been elucidated.PURPOSE:
This study aimed to investigate the reversal effect of DHA on human cervical cancer HeLa cells, and explored its mechanism of action in vitro and in vivo. STUDY DESIGN/METHODS:
The effect and mechanism of DHA on HeLa cells was examined by using CCK-8 assay, flow cytometry, transmission electron microscopy, immunofluorescence, and Western blot analysis in human hepatocellular carcinoma cells.RESULTS:
In this study, it was confirmed that DHA had statistically equivalent anti-tumor efficiency in HeLa cells with a clinical chemotherapeutic agent of cisplatin. Meanwhile, DHA triggered autophagy, where LC3B-II expression was dose-dependently increased. Further, it was revealed that DHA promotes reactive oxygen species (ROS) generation, with DNA double-strand breaks (DSB) damage, as up-regulation of γH2AX protein and foci formation. Interestingly, we firstly demonstrated that DHA induced autophagy through promotion of the phosphorylation of Bcl-2 (Ser70), independent of the phosphorylated JNK1/2 (Thr183/Tyr185). Moreover, DHA-treated HeLa cells displayed an increase in the pro-autophagic protein Beclin-1 with downregulated the phospho-mTOR (Ser2448). Furthermore, upregulated pro-apoptotic protein Bak-1, but not Bax, suggesting Bak-1 is included in DHA-induced autophagy.CONCLUSION:
Therefore, DHA upregulates the phosphorylation of Bcl-2 (Ser70) and mTOR (Ser2448) and induces autophagic cell death in Hela cells. This study provided a mechanism to support DHA, an autophagy inducer, as a potential therapeutic agent for human cervical cancer.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Proteínas Proto-Oncogênicas c-bcl-2
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Artemisininas
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Antimaláricos
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Antineoplásicos
Idioma:
En
Revista:
Phytomedicine
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China