Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple myeloma cells.
Acta Biochim Biophys Sin (Shanghai)
; 53(6): 775-783, 2021 May 21.
Article
in En
| MEDLINE
| ID: mdl-33891090
ABSTRACT
Resveratrol, a natural compound extracted from the skins of grapes, berries, or other fruits, has been shown to have anti-tumor effects against multiple myeloma (MM) via promoting apoptosis and inhibiting cell viability. In addition to apoptosis, autophagy also plays a significant role in anti-tumor effects. However, whether autophagy is involved in anti-MM activity of resveratrol remains unclear. In this study, human MM cell lines U266, RPMI-8226, and NCI-H929 were treated with resveratrol. Cell Counting Kit-8 assay and colony formation assay were used to measure cell viability. Western blot analysis was used to detect apoptosis- and autophagy-associated proteins. 3-Methyladenine (3-MA) was applied to inhibit autophagy. Results showed that resveratrol inhibited cell viability and colony formation via promoting apoptosis and autophagy in MM cell lines U266, RPMI-8226, and NCI-H929. Resveratrol promoted apoptosis-related proteins, Caspase-3 activating poly-ADP-ribose polymerase and Caspase-3 cleavage, and decreased the protein level of Survivin in a dose-dependent manner. Additionally, resveratrol upregulated the levels of LC3 and Beclin1 in a dose-dependent way, indicating that autophagy might be implicated in anti-MM effect of resveratrol. Furthermore, 3-MA relieved the cytotoxicity of resveratrol by blocking the autophagic flux. Resveratrol increased the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream substrates p70S6K and 4EBP1 in a dose-dependent manner, leading to autophagy. Therefore, our results suggest that resveratrol exerts anti-MM effects through apoptosis and autophagy, which can be used as a new therapeutic strategy for MM in clinic.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
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Signal Transduction
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Apoptosis
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AMP-Activated Protein Kinases
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TOR Serine-Threonine Kinases
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Resveratrol
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Multiple Myeloma
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Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Acta Biochim Biophys Sin (Shanghai)
Journal subject:
BIOFISICA
/
BIOQUIMICA
Year:
2021
Document type:
Article
Affiliation country: