Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

Wang, Chongcheng; He, Chuan; Lu, Shan; Wang, Xuanzhong; Wang, Lei; Liang, Shi-peng; Wang, Xinyu; Piao, Meihua; Cui, Jiayue; Chi, Guangfan; Ge, Pengfei

doi:10.1038/s41419-020-02866-3

Cited by 29 publications

(21 citation statements)

References 47 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF. 28 Taken together, our study reveals a key role of hsa_circ_0072309 in regulating autophagy and chemoresistance in p53 dependent manner. Low hsa_circ_0072309 expression predicts poor prognosis for glioma patients.…”

Section: Ack N Owled G Em Entsmentioning

confidence: 56%

See 1 more Smart Citation

Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma

Yuan

Sun

et al. 2022

CNS Neurosci Ther

View full text Add to dashboard Cite

Aims Circular RNAs have been reported to play key roles in the progression of various cancers, including gliomas. The present study was designed to investigate the role of hsa_circ_0072309 in autophagy and temozolomide (TMZ) sensitivity in glioblastoma (GBM). Methods The effect of hsa_circ_0072309 on autophagy and TMZ sensitivity were examined by GFP‐RFP‐LC3, transmission electron microscopy(TEM), flow cytometry, Western blot, and immunofluorescence. The mechanism of hsa_circ_0072309 regulating p53 signaling pathway was analyzed using Western blot, IP, and rescue experiments. Results Low hsa_circ_0072309 expression predicts poor prognosis for glioma patients. The regulation of hsa_circ_0072309 on autophagy and TMZ sensitivity depends on the status of p53. Hsa_circ_0072309 promoted autophagy by p53 signaling pathway and enhanced sensitivity of glioblastoma to temozolomide (TMZ) in p53 wild‐type GBM, but not in p53 mutant GBM. Hsa_circ_0072309 inhibits p53 ubiquitination and increases the stability of p53 protein in the context of p53 wild‐type. MiR‐100 mediates hsa_circ_0072309 regulating p53. P53 inhibitor or autophagy inhibitor could reverse the effect of hsa_circ_0072309 on TMZ sensitivity in p53 wild‐type GBM. Conclusions This study revealed a function of hsa_circ_0072309 promoting autophagy by p53 signaling pathway and enhancing TMZ sensitivity. These findings demonstrated that hsa_circ_0072309 may be a potential and promising target in designing the treatment strategy for GBM.

show abstract

Section: Ack N Owled G Em Entsmentioning

confidence: 56%

“…Olanzapine induced autophagy through suppression of NF‐κB activation in human glioma cells 27 . Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress‐mediated BNIP3‐dependent nuclear translocation of AIF 28 …”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma

Yuan

Sun

et al. 2022

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…In glioma cell lines U87 and U251, silibinin promoted the up-regulated expression of BNIP3, as well as translocation of the protein into the mitochondria by activating autophagy. This, in turn, led to the translocation of AIF from the mitochondria into the nucleus, and ultimately caused cell death ( Wang et al, 2020 ). In breast cancer, silibinin was able to induce autophagy in MCF-7 cells by decreasing Akt/mTOR expression, thus enhancing its inhibitory effect on estrogen receptors and finally causing breast cancer cell death ( Zheng et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway

Bai

Chen

et al. 2022

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Background: Silibinin is widely utilized drug in various cancer treatments, though its application in cholangiocarcinoma has not yet been explored. For the first time, we evaluated the anticancer potential and underlying molecular mechanism of silibinin in treatment of cholangiocarcinoma treatment.Methods: HuCCT-1 and CCLP-1 cells were chosen to be an in vitro study model and were exposed to various concentrations of silibinin for indicated times. Cell viability was evaluated by the cell counting kit-8 (CCK-8) assay and half maximal inhibitory (IC50) concentrations were calculated. Cell proliferation capacity was determined through the use of colony formation and 5-Ethynyl-2′- deoxyuridine (EdU) assays. Cell apoptosis and cycle arrest were assessed by Live/Dead staining assay and flow cytometry (FCM). The protein levels of extracellular regulated protein kinases (ERK)/mitochondrial apoptotic pathway were evaluated through western blotting (WB). Mitochondrial membrane potential changes were determined via 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1). A cholangiocarcinoma cell line xenograft model was used to assess the anti-tumor activity of silibinin in vivo.Results: Inhibition of the ERK protein by silibinin led to a significant decrease in mitochondrial membrane potential, which, in turn, caused Cytochrome C to be released from the mitochondria. The activation of downstream apoptotic pathways led to apoptosis of cholangiocarcinoma cells. In general, silibinin inhibited the growth of cholangiocarcinoma cell line xenograft tumors.Conclusions: Silibinin is able to inhibit cholangiocarcinoma through the ERK/mitochondrial apoptotic pathway, which makes silibinin a potential anti-tumor drug candidate for cholangiocarcinoma treatment.

show abstract

“…Silibinin-induced autophagy increased the mitochondrial accumulation of Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) by augmenting H 2 O 2 levels in cells via depletion of glutathione. In addition, silibinin also induced autophagy-dependent phosphorylation of p53 resulting in apoptosis of glioma cells [ 175 ]. Involvement of autophagy-mediated BNIP3 activation was also observed in breast cancer cells [ 176 ].…”

Section: Roles Of Polyphenols In Autophagic Adaptation For Healthy Agingmentioning

confidence: 99%

Plant Polyphenols for Aging Health: Implication from Their Autophagy Modulating Properties in Age-Associated Diseases

et al. 2021

View full text Add to dashboard Cite

Polyphenols are a family of naturally occurring organic compounds, majorly present in fruits, vegetables, and cereals, characterised by multiple phenol units, including flavonoids, tannic acid, and ellagitannin. Some well-known polyphenols include resveratrol, quercetin, curcumin, epigallocatechin gallate, catechin, hesperetin, cyanidin, procyanidin, caffeic acid, and genistein. They can modulate different pathways inside the host, thereby inducing various health benefits. Autophagy is a conserved process that maintains cellular homeostasis by clearing the damaged cellular components and balancing cellular survival and overall health. Polyphenols could maintain autophagic equilibrium, thereby providing various health benefits in mediating neuroprotection and exhibiting anticancer and antidiabetic properties. They could limit brain damage by dismantling misfolded proteins and dysfunctional mitochondria, thereby activating autophagy and eliciting neuroprotection. An anticarcinogenic mechanism is stimulated by modulating canonical and non-canonical signalling pathways. Polyphenols could also decrease insulin resistance and inhibit loss of pancreatic islet β-cell mass and function from inducing antidiabetic activity. Polyphenols are usually included in the diet and may not cause significant side effects that could be effectively used to prevent and treat major diseases and ailments.

show abstract

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

Cited by 29 publications

References 47 publications

Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma

Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma

Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating ERK/Mitochondrial Pathway

Plant Polyphenols for Aging Health: Implication from Their Autophagy Modulating Properties in Age-Associated Diseases

Contact Info

Product

Resources

About