Apoptin causes apoptosis in<scp>HepG</scp>‐2 cells via Ca<sup>2+</sup>imbalance and activation of the mitochondrial apoptotic pathway

Yu, Xiaoyang; Wang, Tongxing; Li, Yue; Li, Yiquan; Bai, Bing; Fang, Jinbo; Han, Jicheng; Li, Shanzhi; Xiu, Zhiru; Liu, Zirui; Yang, Xia; Zhu, Guangyu; Jin, Ningyi; Shang, Chao; Li, Xiao; Zhu, Yan

doi:10.1002/cam4.5528

Cited by 6 publications

(4 citation statements)

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“…In the ectopic mouse models of HCC, tumor tissue growth was inhibited, DNA damage occurred in cells, and the levels of apoptotic proteins caspase- cells with apoptin for 72 h, 25% apoptosis was observed. The expression levels of cleaved-PARP and cleaved-caspase-3 were signi cantly higher, and the ROS levels in HepG-2 cells were signi cantly increased [22]. The above studies con rm the great potential and application value of apoptin in the treatment of HCC.…”

Section: Discussionsupporting

confidence: 56%

“…Recent studies have identi ed apoptin as a protein precursor drug that is selectively activated in cancer cells through phosphorylation, thereby disrupting the cytoskeleton and promoting cell death [9]. It has also been found that apoptin induces apoptosis in HepG-2 cells via calcium ions, causing an imbalance and activating their mitochondrial apoptotic pathway [10]. The human immunode ciency virus (HIV) trans-activated transcription (TAT) protein, the rst cell-penetrating peptides discovered in 1998 [11], is derived from the human HIV viral TAT protein.…”

Section: Introductionmentioning

confidence: 99%

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A novel recombinant adenovirus expressing apoptin and MEL genes kills hepatocellular carcinoma cells and inhibits the growth and metastasis of ectopic tumors

Wu,

Lan,

et al. 2024

Preprint

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HCC is the most common fatal malignancy. Although surgical resection is the primary treatment strategy, most patients are not eligible for resection due to tumor heterogeneity, underlying liver disease, or comorbidities. Therefore, this study explores the possibility of multi-molecular targeted drug delivery in treating HCC. In this study, we constructed the recombinant adenovirus co-expressing apoptin and melittin (MEL) genes. The inhibitory effect of recombinant adenovirus on hepatocellular carcinoma cells was detected through experiments on cell apoptosis, migration, invasion, and other factors. The tumor inhibitory effect in vivo was assessed using subcutaneous HCC mice. Results showed that recombinant adenovirus co-expressing anti-tumor genes TAT and apoptin, RGD and MEL can significantly inhibit the proliferation, migration, and invasion of HCC cells by inducing an increase in reactive oxygen species (ROS) levels, upregulation of apoptotic proteins such as Bax, caspase-3, and caspase-9, and downregulation of the anti-apoptotic protein Bcl2. In subcutaneous HCC mice, recombinant adenovirus induced significant apoptosis in tumor cells, inhibited tumor growth. In conclusion, recombinant adenovirus co-expressing apoptin and MEL can inhibit the growth and proliferation of tumor cells both in vivo and in vitro.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

A novel recombinant adenovirus expressing apoptin and MEL genes kills hepatocellular carcinoma cells and inhibits the growth and metastasis of ectopic tumors

Wu,

Lan,

et al. 2024

Preprint

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“…Calcium overload within mitochondria fails to maintain average mitochondrial membrane potential, leading to mitochondrial dysfunction. 23 Flow cytometry analysis revealed a significant increase in MMP in the Sur+Ru360 group compared with the Sur group and Sur+ saline group ( Figures 5E and F ). Surgery resulted in a decrease in mitochondrial membrane potential in hippocampal neurons ( Figures 5E and F ).…”

Section: Resultsmentioning

confidence: 92%

Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial Dysfunction

Xu¹,

Zhou²,

Liu³

et al. 2023

NDT

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Purpose Ru360, a selective inhibitor of mitochondrial calcium uptake, maintains mitochondrial calcium homeostasis. To evaluate whether mitochondrial calcium uniporter (MCU)-mediated mitochondrial function is associated with the pathological process of Postoperative cognitive dysfunction (POCD), elucidate its relationship with neuroinflammation, and observe whether the relevant pathological process can be improved with Ru360. Methods Aged mice underwent experimental open abdominal surgery after anesthesia. Open field tests, Novel object recognition tests and Y Maze Tests were used to conduct behavioral experiments. The reactive oxygen species (ROS) content, the levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), intra-mitochondrial calcium, mitochondrial membrane potential (MMP) and the activity of antioxidant superoxide dismutase (SOD) in the hippocampus of mice were detected using kits. The expression of proteins was detected using Western blot. Results After treatment with Ru360, MCU-mediated mitochondrial dysfunction was inhibited, neuroinflammation was reduced, and the learning ability of the mice was improved after surgery. Conclusion Our study demonstrated that mitochondrial function plays a crucial role in the pathology of POCD, and using Ru360 to improve mitochondrial function may be a new and necessary direction for the treatment of POCD.

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“…SARS-CoV-2 ORF 3a interferes with calcium homeostasis and induces autophagy to enhance viral infection ( Garrido-Huarte et al, 2023 ). Calcium imbalance triggers the mitochondrial apoptotic pathway to promote infection by chicken anemia virus ( Yu et al, 2023 ). Herpes simplex virus (HSV) infection induces a rapid increase in the intracellular calcium ion concentration, which plays a key role in facilitating virus entry ( Jiang et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells

Kan,

Zhang,

Liao

et al. 2023

Front. Microbiol.

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Porcine epidemic diarrhea virus (PEDV) mainly invades the small intestine and promotes an inflammatory response, eventually leading to severe diarrhea, vomiting, dehydration, and even death of piglets, which seriously threatens the economic development of pig farming. In recent years, researchers have found that probiotics can improve the intestinal microenvironment and reduce diarrhea. At the same time, certain probiotics have been shown to have antiviral effects; however, their mechanisms are different. Herein, we aimed to investigate the inhibitory effect of Lactiplantibacillus plantarum supernatant (LP-1S) on PEDV and its mechanism. We used IPEC-J2 cells as a model to assess the inhibitory effect of LP-1S on PEDV and to further investigate the relationship between LP-1S, Ca2+, and PEDV. The results showed that a divalent cation chelating agent (EGTA) and calcium channel inhibitors (Bepridil hydrochloride and BAPTA-acetoxymethylate) could inhibit PEDV proliferation while effectively reducing the intracellular Ca2+ concentration. Furthermore, LP-1S could reduce PEDV-induced loss of calcium channel proteins (TRPV6 and PMCA1b), alleviate intracellular Ca2+ accumulation caused by PEDV infection, and promote the balance of intra- and extracellular Ca2+ concentrations, thereby inhibiting PEDV proliferation. In summary, we found that LP-1S has potential therapeutic value against PEDV, which is realized by modulating Ca2+. This provides a potential new drug to treat PEDV infection.

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Apoptin causes apoptosis inHepG‐2 cells via Ca²⁺imbalance and activation of the mitochondrial apoptotic pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 6 publications

References 43 publications

A novel recombinant adenovirus expressing apoptin and MEL genes kills hepatocellular carcinoma cells and inhibits the growth and metastasis of ectopic tumors

A novel recombinant adenovirus expressing apoptin and MEL genes kills hepatocellular carcinoma cells and inhibits the growth and metastasis of ectopic tumors

Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial Dysfunction

Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells

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Apoptin causes apoptosis inHepG‐2 cells via Ca2+imbalance and activation of the mitochondrial apoptotic pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 6 publications

References 43 publications

A novel recombinant adenovirus expressing apoptin and MEL genes kills hepatocellular carcinoma cells and inhibits the growth and metastasis of ectopic tumors

A novel recombinant adenovirus expressing apoptin and MEL genes kills hepatocellular carcinoma cells and inhibits the growth and metastasis of ectopic tumors

Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial Dysfunction

Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells

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Apoptin causes apoptosis inHepG‐2 cells via Ca²⁺imbalance and activation of the mitochondrial apoptotic pathway