The Role of the Hematopoietic Cell-Specific Protein 1-Associated Protein X-1 in Human Papillomavirus 16 E2-Induced Human Cervical Squamous Carcinoma Cell Apoptosis via a Mitochondria-Dependent Pathway

2021 ◽  
pp. 1-10
Author(s):  
Hui Gong ◽  
Ping Wang ◽  
Ming Yu ◽  
Yu Zhu ◽  
Lichen Teng ◽  
...  

<b><i>Objectives:</i></b> Human papillomavirus 16 (HPV 16) E2 is a transcriptional regulator that plays a key role in regulating a variety of biological responses. Hematopoietic cell-specific protein 1-related protein X-1 (HAX-1) is a mitochondrial membrane protein, and the HAX-1 gene is involved in the occurrence, growth, invasion, and metastasis of various human malignant tumors. The purpose of this study was to investigate the relationships among HPV 16 E2, the role of HAX-1 gene, and the underlying intracellular apoptotic mechanism of human cervical squamous carcinoma cells (C33a and SiHa). <b><i>Methods:</i></b> In this study, HAX-1 expression was examined using real-time polymerase chain reaction, Western blot, and immunohistochemical staining analysis. Apoptosis of cells was assessed by flow cytometry. The mitochondrial function was assessed by the mitochondrial copy number, reactive oxygen species (ROS) generation, the mitochondrial membrane potential (ΔΨm), and mitochondrial morphology. <b><i>Results:</i></b> Our study demonstrated that the expression of the HAX-1 gene was significantly increased in human cervical carcinoma tissues relative to noncancerous cervix tissues. HPV 16 E2 inhibited HAX-1 protein expression. Overexpression of HAX-1 increased the mitochondrial copy number, decreased the production of ROS, and maintained the integrity of the mitochondrial membrane and morphology. So, enhanced expression of the HAX-1 gene could abrogate the HPV 16 E2-induced cell apoptosis. <b><i>Conclusion:</i></b> Therefore, these data support a mechanism that HAX-1 plays a crucial role in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis in a mitochondrial-dependent manner.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Piyawat Tangsuksan ◽  
Jureeporn Chuerduangphui ◽  
Chutha Takahashi Yupanqui ◽  
Teerapol Srichana ◽  
Ekarat Hitakomate ◽  
...  

Abstract Background Oral cancer is often preceded by a mucosal lesion called an oral potentially malignant disorder (OPMD). Many plant-derived compounds are of value in medicine. The objectives of this study were to develop a soluble mucoadhesive film containing α-mangostin (α-MG), a compound extracted from the peel of mangosteen fruit, and determine its activities against oral cancer cells, against human papillomavirus type 16 (HPV-16) pseudovirus, and its anti-inflammatory properties. Methods A soluble mucoadhesive film containing α-MG was prepared. Oral squamous carcinoma cell line (SCC25), murine macrophage cells (RAW264.7), and human gingival fibroblast cell line were cultured. Anticancer activity and viability of SCC25 cells in response to α-MG film solution were determined by MTT assay. HPV-16 pseudovirus was constructed and effects of the film solution on attachment and post-attachment steps of the infection were investigated. Anti-inflammatory activity was assessed by nitric oxide (NO) inhibition. Fibroblast cell migration was determined by in vitro scratch assay. Results The soluble α-MG film showed cytotoxic effects on SCC25 cells in concentration > 125 µg/ml with IC50 of 152.5 µg/ml. Antiviral activity against HPV-16 pseudovirus was observed at attachment step, but not at post-attachment step. The film also possessed a strong anti-inflammatory effect and promoted wound healing without cytotoxicity. Conclusions Mucoadhesive film containing α-MG has a cytotoxic effect on oral squamous carcinoma cell line and an inhibitory effect on HPV-16 pseudovirus at attachment step. The α-MG film also shows a potent anti-inflammatory activity and enhances wound healing. Thus, the soluble α-MG film may have a potential role in treating oral cancer.


2021 ◽  
Vol 11 (9) ◽  
pp. 1844-1847
Author(s):  
DaoBin Lin ◽  
Zhangkai Yang ◽  
YiHua Su ◽  
YaWei Cheng

Carvacrol is a natural phenol with antioxidant, antimicrobials, and anti-cancer activities. The present study aimed to explore the anti-cancer activity of carvacrol in human esophageal squamous carcinoma KYSE-150 cells. Cell proliferation and apoptosis were measured using WST-1 assay and cell death detection ELISA kit respectively. Caspase activities were determined with caspase fluorometric assay kits. WST-1 assay revealed that carvacrol suppressed KYSE-150 cell proliferation in both dose and time-dependent manner. Carvacrol could increase cell apoptosis in a dose-dependent manner through caspase-3 and caspase-9 activation. In addition, Bcl-2 mRNA levels were significantly decreased by carvacrol treatment. This study delivers that carvacrol exerts a favorable anti-cancer action against esophageal cancer via inhibiting cell proliferation and inducing cell apoptosis. These discoveries suggest that carvacrol is deserved to be further studied and developed as a chemotherapeutic agent for esophageal cancer.


2018 ◽  
Vol 49 (5) ◽  
pp. 2022-2034 ◽  
Author(s):  
Weiwei Xia ◽  
Jie Yin ◽  
Shuping Zhang ◽  
Chuchu Guo ◽  
Yuanyuan Li ◽  
...  

Background/Aims: Although a number of reports documented the important role of parkin in mitophagy, emerging evidence also indicated additional functions of parkin besides mitophagy. The present study was undertaken to investigate the role of parkin in the regulation of ERRα/eNOS pathway in endothelial cells (ECs). Methods: Mouse aortic endothelial cells (MAECs) and cardiac muscle HL-1 cells were transfected with parkin plasmid or siRNA. ERRα inhibitor XCT-790, autophagy inhibitor 3-MA and Bafilomycin A1, and caspase inhibitor Z-VAD-FMK were used to block autophagy or apoptosis. Western blotting was performed to examine the protein levels. Flow cytometry was applied to determine the cell apoptosis and ROS production. Mitochondrial membrane potential was measured using JC-1 and TMRM. Immunoprecipitation was performed to confirm the parkin effect on ERRα ubiquitination. Results: Overexpression of parkin resulted in a significant reduction of total-eNOS and p-eNOS in parallel with the downregulation of ERRα (a regulator of eNOS) protein and the enhancement of ERRα ubiquitination. To test the role of ERRα in regulating eNOS in this experimental setting, we treated ECs with ERRα inhibitor and found a decrement of total-eNOS and p-eNOS. On the contrary, overexpression of ERRα increased the levels of total-eNOS and p-eNOS. Meanwhile, parkin overexpression induced mitochondrial dysfunction and cell apoptosis in both ECs and HL-1 cells. Finally, we confirmed that the parkin effect on the regulation of eNOS was independent of the autophagy and apoptosis. Conclusion: These findings suggested that parkin overexpression downregulated eNOS possibly through the ubiquitination of ERRα in endothelial cells.


2019 ◽  
Vol 72 (8) ◽  
pp. 1566-1570
Author(s):  
Mateusz Mizgalski ◽  
Krzysztof Zub ◽  
Karolina Dorobisz ◽  
Tomasz Zatoński

Epidemiological studies correlate sun or UV light exposure with a lower incidence of a variety of malignancies, including breast, colon and prostate cancer. The biologically active 1,25(OH)2D3 and its analogs have been shown to have antiproliferative and differentiating effects in a variety of malignant and non-malignant cells. The effects of 1,25(OH)2D3 are mediated by the binding of calcitriol to a specific intracellular receptor, vitamin D receptor [VDR]. The aim of this study is to review the literature concerning the role of 1,25(OH)2D3 and its analogs in squamous carcinoma cell lines of the head and neck (SCCHN).


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