Autophagy and cancer: Can tetrandrine be a potent anticancer drug in the near future?

Bhagya, N.; Chandrashekar, K. R.

doi:10.1016/j.biopha.2022.112727

Cited by 27 publications

(19 citation statements)

References 116 publications

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“…To investigate the mechanism of the inhibitory effects of tetrandrine on myogenesis, we reviewed previous reports about tetrandrine and its association with myogenesis [ 10 , 23 , 24 ]. Because regulated autophagy levels are essential for myogenesis [ 25 ] and tetrandrine can efficiently activate autophagy in cancer cells [ 26 ], we hypothesized that tetrandrine could affect myogenesis by regulating autophagy.…”

Section: Resultsmentioning

confidence: 99%

“…It has been shown that tetrandrine can upregulate the expression of autophagy proteins, such as LC3 I/II and SQSTM1/p62, in cancer cells, suggesting that it can activate autophagy [ 7 , 23 , 26 , 39 ]. There have been reports show that tetrandrine can also inhibit autophagy by blocking the late stage of autophagic flux, which is driven by the deacidification of lysosomes [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

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Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Shi

Liu

et al. 2022

IJMS

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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 BaCl2-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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Shi

Liu

et al. 2022

IJMS

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“…Amiodarone, an inhibitor of the myocardial Ca 2+ , K + and Na + channels (Kodama et al, 1999), did not show significant inhibition of any of the fusion. Tetrandrine is a natural compound which blocks Ca 2+ channel amongst its multi-inhibitory activity (Bhagya and Chandrashekar, 2022). It potently inhibited fusion luciferase activity in all other conditions (Figure 6, Supplementary Figure S12); however, this could be partly accounted for by its cytotoxicity (Figure 6).…”

Section: Different Modes Of Fusion Display Different Calcium Dependencymentioning

confidence: 99%

Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation

Chan

2022

Front. Pharmacol.

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Virus fusion process is evolutionarily conserved and provides a promising pan-viral target. Cell-cell fusion leads to syncytial formation and has implications in pathogenesis, virus spread and immune evasion. Drugs that target these processes can be developed into anti-virals. Here, we have developed sensitive, rapid, adaptable fusion reporter gene assays as models for plasma membrane and alternative fusion pathways as well as syncytial fusion in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have confirmed their specificity using neutralizing antibodies and specific protease inhibitors. The fusion report gene assays are more sensitive and unbiased than morphological fusion assay. The fusion assays can differentiate between transmembrane serine protease 2 (TMPRSS2)-dependency in TMPRSS2(+) cells and trypsin-dependency in angiotensin-converting enzyme 2 (ACE2)(+)TMPRSS2(-) cells. Moreover, we have identified putative novel fusion processes that are triggered by an acidic pH with and without trypsin. Coupled with morphological fusion criteria, we have found that syncytia formation is enhanced by TMPRSS2 or trypsin. By testing against our top drug hits previously shown to inhibit SARS-CoV-2 pseudovirus infection, we have identified several fusion inhibitors including structurally related lopsided kite-shaped molecules. Our results have important implications in the development of universal blockers and synergistic therapeutics and the small molecule inhibitors can provide important tools in elucidating the fusion process.

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“…Tetrandrine (TET) has been shown to exert anti-cancer properties via targeting autophagy, according to a recent review [ 125 ]. TET induces autophagy in tumor cells by increasing the accumulation of ROS.…”

Section: Natural Products Overcome Autophagy-mediated Tumor Drug Resi...mentioning

confidence: 99%

Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective

Yao

Feng

et al. 2022

Biomolecules

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Autophagy is a critical cellular adaptive response in tumor formation. Nutritional deficiency and hypoxia exacerbate autophagic flux in established malignancies, promoting tumor cell proliferation, migration, metastasis, and resistance to therapeutic interventions. Pro-survival autophagy inhibition may be a promising treatment option for advanced cancer. Furthermore, excessive or persistent autophagy is cytotoxic, resulting in tumor cell death. Targeted autophagy activation has also shown significant promise in the fight against tumor drug resistance. Several research groups have examined the ability of natural products (NPs) such as alkaloids, terpenoids, polyphenols, and anthraquinones to serve as autophagy inhibitors or activators. The data support the capacity of NPs that promote lethal autophagy or inhibit pro-survival autophagy from being employed against tumor drug resistance. This paper discusses the potential applications of NPs that regulate autophagy in the fight against tumor drug resistance, some limitations of the current studies, and future research needs and priorities.

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Autophagy and cancer: Can tetrandrine be a potent anticancer drug in the near future?

Cited by 27 publications

References 116 publications

Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation

Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective

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