TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells

Zhang, Xuan; Zhang, Meilan; Xiao, Bin; Jiao, Wenjun; Zhang, Silin; Zhang, Xuewu

doi:10.3892/or.2018.6196

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…Therefore, we detected a stemness-destructed autophagy induced by mTOR inhibitors, which is supported by previous studies 23 , 24 . Although other studies suggests that autophagy is protective 39 , 40 , we argue that tumor cells have to derive adequate nutrient substance to guarantee basic survival-related sustainment upon various stresses by sacrificing some aggressive behaviors, such as stemness maintenance. Similarly, we detected that mTOR inhibitors, an autophagy inducer, exerted an effect of suppression on the self-renewal and tumorigenicity of GICs and could be blocked by using autophagy inhibitors in vitro.…”

Section: Discussionmentioning

confidence: 67%

Autophagy suppresses self-renewal ability and tumorigenicity of glioma-initiating cells and promotes Notch1 degradation

Tao

et al. 2018

Cell Death Dis

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Autophagy is a vital process that involves degradation of long-lived proteins and dysfunctional organelles and contributes to cellular metabolism. Glioma-initiating cells (GICs) have the ability to self-renew, differentiate into heterogeneous types of tumor cells, and sustain tumorigenicity; thus, GICs lead to tumor recurrence. Accumulating evidence indicates that autophagy can induce stem cell differentiation and increase the lethality of temozolomide against GICs. However, the mechanism underlying the regulation of GIC self-renewal by autophagy remains uncharacterized. In the present study, autophagy induced by AZD8055 and rapamycin treatment suppressed GIC self-renewal in vitro. We found that autophagy inhibited Notch1 pathway activation. Moreover, autophagy activated Notch1 degradation, which is associated with maintenance of the self-renewal ability of GICs. Furthermore, autophagy abolished the tumorigenicity of CD133 + U87-MG neurosphere cells in an intracranial model. These findings suggest that autophagy regulating GICs self-renewal and tumorigenicity is probably bound up with Notch1 degradation. The results of this study could aid in the design of autophagy-based clinical trials for glioma treatments, which may be of great value.

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Section: Discussionmentioning

confidence: 67%

Autophagy suppresses self-renewal ability and tumorigenicity of glioma-initiating cells and promotes Notch1 degradation

Tao

et al. 2018

Cell Death Dis

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“…Previous studies have reported that activating the Akt/mTOR signaling pathway promotes inflammation and apoptosis; on the contrary, inhibiting the Akt/mTOR signaling pathway can alleviate the occurrence of inflammation in hµMan liver cancer cells [21]. Data show that platycodin D treatment diminished phosphorylation of PI3K/Akt/mTOR signaling pathway in A549 and the NCI-H460 cells [22].…”

Section: Discussionmentioning

confidence: 85%

Platycodin D Alleviates High-Glucose-Aggravated Inflammatory Responses in Oral Mucosal Cells by PI3K/mTOR Pathway

et al. 2022

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Oral mucosal diseases account for an increasing proportion of hμMan diseases. Among the many common risk factors that cause oral diseases and systemic diseases, dietary factors, especially high sugar, are particularly prominent. Exhibiting therapeutic potential in treating certain inflammation-related diseases, platycodin D (PD) has been known to possess anti-inflammatory benefits in cases of cytokine-induced inflammation, a fact that has been widely docμMented. However, there are few studies about PD in the oral mucosal disease. Investigating the effect of PD on high-glucose (HG)-induced inflammatory responses in oral mucosal cells was the endeavor of this study. The results revealed that HG induced cell mortality, promoted activity of inflammatory factor (TNF-α, IL-1β, IL-6, and IL-8), and increased ROS production in oral mucosal cells. Interestingly, PD obviously alleviated HG-induced oral mucosal cells inflammatory response. Simultaneously, the expressions of PI3K and mTOR were inhibited by PD. In addition, the activation of PI3K and mTOR decreased the protective effect of PD on oral mucosal cells. To conclude, the PI3K/mTOR signaling pathway was found to be inactivated, thereby restraining the activation of the full immune cell by inhibition of the pro-inflammatory cytokines, as revealed by the results indicating the prevention of the HG-induced inflammation response by PD.

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“…Consistently, we found that autophagy was inhibited in ASPP2 haploinsufficient (ASPP2 +/− ) mice after 70% PH X , indicating that ASPP2 may promote autophagy. Considering that mTORC1 is one of the upstream regulators of autophagy 27–29 and that ASPP2 regulates mTORC1, we speculated that ASPP2 may regulate autophagy through the mTORC1 pathway, which may be a novel finding that warrants further exploration.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of apoptosis-stimulating protein two of p53 promotes liver regeneration in mice by activating mammalian target of rapamycin

Shi

Zhang

et al. 2018

Sci Rep

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Although liver regeneration has been intensively studied in various ways, the mechanisms underlying liver regeneration remain elusive. Apoptosis-stimulating protein two of p53 (ASPP2) was discovered as a binding partner of p53 and plays an important role in regulating cell apoptosis and growth. However, the role of ASPP2 in hepatocyte proliferation and liver regeneration has not been reported. The expression profile of ASPP2 was measured in a mouse model with 70% partial hepatectomy (PHX). Liver regeneration and hepatocyte proliferation were detected in wild-type (ASPP2+/+) and ASPP2 haploinsufficient (ASPP2+/−) mice with PHX. The mammalian target of rapamycin (mTOR) and autophagy pathways were analyzed in the ASPP2+/+ and ASPP2+/− mice with PHX. After rapamycin or 3-methyladenine (3-MA) treatment, hepatocyte proliferation and liver regeneration were analyzed in the ASPP2+/+ and ASPP2+/− mice with PHX. ASPP2 expression was shown to be upregulated at the early stage and downregulated at the late stage. Compared to the ASPP2+/+ mice, liver regeneration was enhanced in ASPP2+/− mice with 70% PHX. In addition, compared to the ASPP2+/+ mice, the mTORC1 pathway was significantly upregulated and the autophagic pathway was downregulated in ASPP2+/−mice with 70% PHX. Inhibition of the mTORC1 pathway significantly suppressed liver regeneration in ASPP2+/− mice with 70% PHX. In contrast, disruption of the autophagic pathway further enhanced liver regeneration in ASPP2+/− mice with 70% PHX. ASPP2 deficiency can promote liver regeneration through activating the mTORC1 pathway, which further regulates downstream molecules, such as those related to autophagy and p70S6K expression in mouse model post-PHX.

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TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells

Cited by 7 publications

References 28 publications

Autophagy suppresses self-renewal ability and tumorigenicity of glioma-initiating cells and promotes Notch1 degradation

Autophagy suppresses self-renewal ability and tumorigenicity of glioma-initiating cells and promotes Notch1 degradation

Platycodin D Alleviates High-Glucose-Aggravated Inflammatory Responses in Oral Mucosal Cells by PI3K/mTOR Pathway

Deficiency of apoptosis-stimulating protein two of p53 promotes liver regeneration in mice by activating mammalian target of rapamycin

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