Apoptin Regulates Apoptosis and Autophagy by Modulating Reactive Oxygen Species (ROS) Levels in Human Liver Cancer Cells

Li, Yiquan; Zhu, Yan; Fang, Jinbo; Li, Wenjie; Li, Shanzhi; Liu, Xing; Liu, Zirui; Song, Gaojie; Shang, Chao; Cong, Jianan; Bai, Bing; Sun, Lili; Jin, Ningyi; Li, Xiao

doi:10.3389/fonc.2020.01026

Cited by 14 publications

(7 citation statements)

References 48 publications

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“…Apoptosis, necrosis, and autophagy have been shown to be related to apoptin induced cell death. Apoptin induced cell death is caused by the mitochondrial apoptosis pathway and the ROS pathway [10,11]. In this study, we confirmed that apoptin triggers another type of programmed cell death (PCD), named pyroptosis, via the ROS pathway.…”

Section: Introductionsupporting

confidence: 64%

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Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway

Liu¹,

Li²,

Zhu³

et al. 2022

Int. J. Biol. Sci.

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Apoptin is a small molecular weight protein encoded by the VP3 gene of chicken anemia virus (CAV). It can induce apoptosis of tumor cells and play anti-tumorigenic functions. In this study, we identified a time-dependent inhibitory role of apoptin on the viability of HCT116 cells. We also demonstrated that apoptin induces pyroptosis through cleaved caspase 3, and with a concomitant cleavage of gasdermin E (GSDME) rather than GSDMD. GSDME knockdown switched the apoptin-induced cell death from pyroptosis to apoptosis in vitro. Furthermore, we demonstrated that the effect of apoptin on GSDME-dependent pyroptosis could be mitigated by caspase-3 and caspase-9 siRNA knockdown. Additionally, apoptin enhanced the intracellular reactive oxygen species (ROS), causing aggregation of the mitochondrial membrane protein Tom20. Moreover, bax and cytochrome c were released to the activating caspase-9, eventually triggering pyroptosis. Therefore, GSDME mediates the apoptin-induced pyroptosis through the mitochondrial apoptotic pathway. Finally, using nude mice xenografted with HCT116 cells, we found that apoptin induces pyroptosis and significantly inhibits tumor growth. Based on this mechanism, apoptin may provide a new strategy for colorectal cancer therapy.

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Section: Introductionsupporting

confidence: 64%

“…It has been reported that apoptin can significantly inhibit the growth of liver cancer cells by causing cell apoptosis [11]. We also want to explore whether ROS are involved in apoptin induced pyroptosis.…”

Section: Apoptin Induced Pyroptosis Through the Ros Pathwaymentioning

confidence: 99%

Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway

Liu¹,

Li²,

Zhu³

et al. 2022

Int. J. Biol. Sci.

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“…In response to oxidative stress, cells may turn on autophagy and apoptosis [ 44 ], which may interact with each other [ 45 ]. To address this concern, Baf A1 was applied to assess the impact of autophagy on PHA-triggered apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells

Shiau

Tang

et al. 2022

Antioxidants

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Physalis peruviana-derived physapruin A (PHA) is a potent compound that selectively generates reactive oxygen species (ROS) and induces cancer cell death. Autophagy, a cellular self-clearance pathway, can be induced by ROS and plays a dual role in cancer cell death. However, the role of autophagy in PHA-treated cancer cells is not understood. Our study initially showed that autophagy inhibitors such as bafilomycin A1 enhanced the cytotoxic effects of PHA in breast cancer cell lines, including MCF7 and MDA-MB-231. PHA treatment decreased the p62 protein level and increased LC3-II flux. PHA increased the fluorescence intensity of DAPGreen and DALGreen, which are used to reflect the formation of autophagosome/autolysosome and autolysosome, respectively. ROS scavenger N-acetylcysteine (NAC) decreased PHA-elevated autophagy activity, implying that PHA-induced ROS may be required for autophagy induction in breast cancer cells. Moreover, the autophagy inhibitor increased ROS levels and enhanced PHA-elevated ROS levels, while NAC scavenges the produced ROS resulting from PHA and autophagy inhibitor. In addition, the autophagy inhibitor elevated the PHA-induced proportion of annexin V/7-aminoactinmycin D and cleavage of caspase-3/8/9 and poly (ADP-ribose) polymerase. In contrast, NAC and apoptosis inhibitor Z-VAD-FMK blocked the proportion of annexin V/7-aminoactinmycin D and the activation of caspases. Taken together, PHA induced ROS to promote autophagy, which might play an antioxidant and anti-apoptotic role in breast cancer cells.

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“… 18 The number of men with liver cancer in China is second only to that with lung cancer, whereas the number of women with liver cancer is second only to that with breast cancer. 19 Patients with HCC are often diagnosed when the disease is at an advanced stage, and many patients continue to die from disease recurrence and distant metastasis after surgery. Therefore, there is an urgent need to find more effective biomarkers for early diagnosis and surveillance of the development of liver cancer.…”

Section: Discussionmentioning

confidence: 99%

CENPO is Associated with Immune Cell Infiltration and is a Potential Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

He¹,

Xie²,

Li³

et al. 2022

IJGM

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Purpose To examine the expression, clinical significance, and potential regulatory mechanism of centromere protein O (CENPO) in hepatocellular carcinoma (HCC). Methods CENPO expression in pan-cancer was studied using the TCGA-GTEx database, in HCC and normal liver tissues using the GEO and TCGA databases, and in clinical HCC samples by RT-qPCR. The diagnostic value of CENPO was assessed using receiver operating characteristic curves. Univariate and multivariate regression analyses of factors associated with HCC prognosis were performed. CENPO function and its mechanism in HCC were explored using GO, KEGG, and GSEA analyses of differentially expressed genes (DEGs). Association of CENPO expression with immune cell infiltration and immune checkpoint-associated molecules was conducted using TCGA data and the TIMER2.0 database. Relationships between CENPO expression and DNA methylation were analyzed using the UALCAN and cBioPortal databases. CENPO expression in HCC cell lines was detected using RT-qPCR. Results CENPO is upregulated in most cancers, including HCC and cell lines, and is a potential biomarker for HCC diagnosis (AUC = 0.936, 95% CI: 0.911–0.960). Higher CENPO expression was associated with poorer outcomes in patients with HCC (OS, p = 0.004; DSS, p = 0.002; PFI, p < 0.001), and CENPO was an independent predictor of factors influencing overall survival in HCC. DEGs between samples with high and low CENPO levels were enriched in various biological processes, including activation of the G2M checkpoint and other signaling pathways, while CENPO expression correlated with HCC immune cell infiltration and immune checkpoint-associated molecules, as well as CENPO promoter methylation (p < 0.001). Conclusion In HCC and cell lines, CENPO is overexpressed, a potential diagnostic marker and an indicator of poor prognosis. CENPO may regulate HCC development by influencing nuclear division and tumor immune infiltration and is regulated by methylation, making it a potential target for HCC immunotherapy.

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Apoptin Regulates Apoptosis and Autophagy by Modulating Reactive Oxygen Species (ROS) Levels in Human Liver Cancer Cells

Cited by 14 publications

References 48 publications

Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway

Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway

Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells

CENPO is Associated with Immune Cell Infiltration and is a Potential Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

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