ReferenceID 2975
Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux
Int J Mol Sci
Tetrandrine is well known to act as a calcium channel blocker. It is a potential candidate for a tumor chemotherapy drug without toxicity. Tetrandrine inhibits cancer cell proliferation and induces cell death through apo
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Record Fields
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- Reference Id
- 2975
- Evidence Id
- 19565
- Core Evidence Id
- 19565
- Source Reference Id
- 5951
- Herb2 Reference Id
- HBREF006748
- Subject Paper Key
- HBIN046110_35897724
- Pubmed Id
- 35897724
- Doi
- 10.3390/ijms23158148
- Paper Title
- Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux
- Paper Abstract
- Tetrandrine is well known to act as a calcium channel blocker. It is a potential candidate for a tumor chemotherapy drug without toxicity. Tetrandrine inhibits cancer cell proliferation and induces cell death through apoptosis and autophagy. As cancer patients usually experience complications with sarcopenia or muscle injury, we thus assessed the effects of tetrandrine on skeletal muscle cells. We report in this study that a low dose of tetrandrine (less than 5 μM) does not affect the proliferation of C2C12 myoblasts, but significantly inhibits myogenic differentiation. Consistently, tetrandrine inhibited muscle regeneration after BaCl 2 -induced injury. Mechanistic experiments showed that tetrandrine decreased the p-mTOR level and increased the levels of LC3 and SQSTM1/p62 during differentiation. Ad-mRFP-GFP-LC3B transfection experiments revealed that the lysosomal quenching of GFP signals was suppressed by tetrandrine. Furthermore, the levels of DNM1L/Drp1, PPARGA1 and cytochrome C (Cyto C), as well as caspase 3 activation and ROS production, were decreased following tetrandrine administration, indicating that the mitochondrial network signaling was inhibited. Our results indicate that tetrandrine has dual effects on autophagic flux in myoblasts during differentiation, activation in the early stage and blockade in the late stage. The ultimate blocking of autophagic flux by tetrandrine led to the disruption of mitochondria remodeling and inhibition of myogenic differentiation. The inhibitory effects of tetrandrine on skeletal muscle differentiation may limit its application in advanced cancer patients. Thus, great attention should be paid to the clinical use of tetrandrine for cancer therapy.
- Journal
- Int J Mol Sci
- Publish Year
- 2022
- Experiment Subject
- patient; c2c12 myoblasts
- Experiment Type
- Cell Experiment
- Phenotype Related
- Sarcopenia; Tumor; Advanced Cancer; Muscle Injury; Cancer
- Paper Title Cn
- Paper Title En
- Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux
- Bilingual Status
- semi_complete