scholarly journals REG γ knockdown suppresses proliferation by inducing apoptosis and cell cycle arrest in osteosarcoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8954
Author(s):  
Zhiqiang Yin ◽  
Hao Jin ◽  
Shibo Huang ◽  
Guofan Qu ◽  
Qinggang Meng
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Western Blotting ◽  
Caspase 3 ◽  
Cell Counting ◽  
Osteosarcoma Cells ◽  
Cycle Arrest

Background Osteosarcoma (OS) is the most common malignant bone tumor with high mortality in children and adolescents. REG γ is overexpressed and plays oncogenic roles in various types of human cancers. However, the expression and potential roles of REG γ in osteosarcoma are elusive. This study aims at exploring possible biological functions of REG γ in the pathogenesis of osteosarcoma and its underlying mechanism. Methods Quantitativereverse transcription-polymerase chain reaction (qRT-PCR), western blotting andimmunohistochemistry (IHC)were performed to detect the expression levels of REG γ in OS tissues and cell lines. Then, the effects of REG γ expression on OS cell proliferation in vitro were analyzed by Cell Counting Kit-8 (CCK-8), ethylene deoxyuridine (EdU), colony formation, flow cytometry. The protein levels of apoptosis and cell-cycle related proteins were evaluated using western blotting. Results In present study, we found for the first time that REG γ is overexpressed in osteosarcoma tissues and cell lines and knockdown of REG γ significantly inhibits cell proliferation and induces apoptosis and cell cycle arrest in osteosarcoma cells. Furthermore, we observed that p21, caspase-3 and cleaved caspase-3 are increased while the expression of cycinD1 and bcl-2 are decreased after REG γ depletion in osteosarcoma cells. In conclusion, REG γ may be involved in the proliferation of osteosarcoma and serve as a novel therapeutic target in patients with osteosarcoma.

scholarly journals Lenvatinib Inhibits Intrahepatic Cholangiocarcinoma Growth via Gadd45a-Mediated Cell Cycle Arrest

2021 ◽  
Author(s):  
Xia Yan ◽  
Dan Wang ◽  
Liping Zhuang ◽  
Peng Wang ◽  
Zhiqiang Meng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Intrahepatic Cholangiocarcinoma ◽  
Primary Liver Cancer ◽  
Transcriptional Profiling ◽  
Cycle Arrest

Abstract Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer, and its 5-year survival rate is less than 10%. Fibroblast growth factor receptor (FGFR) changes have been observed in 6%-50% of ICC patients, and patients with FGFR mutations have been shown to have more inert tumour biological activity than patients with wild-type FGFRs. Thus, as a pan-FGFR inhibitor, lenvatinib is supposed to play an anti-tumour role in ICC. However, no relevant experiments have been reported.Methods: Patients derived xenograft (PDX) model and cell line derived xenograft (CDX) model were both used for the in vivo study. For in vivo work, ICC cell lines were applied to analyse the effect of Lenvatinib on cell proliferation, cell cycle progression, apoptosis, and the molecular mechanism.Reaults: In the present study, we found that lenvatinib dramatically hindered in vivo tumor growth in ICC patient-derived xenograft models. In addition, by using in vitro experiments in ICC cell lines, we found that lenvatinib dose- and time-dependently inhibited the proliferation of ICC cells and induced cell cycle arrest in the G0/G1 phase. Transcriptional profiling analysis further applied indicated that lenvatinib might inhibit cell proliferation through the induction of cell-cycle arrestment via activating of Gadd45a, it was evidenced by that the knockout of Gadd45a significantly attenuated the cycle arrest induced by lenvatinib, as well as the inhibitory effect of lenvatinib on ICC.Conclusion: Our work firstly found that lenvatinib exerted excellent antitumor effect on ICC, mainly via inducing Gadd45a mediated cell cycle arrest. Our work provides evidence and a rationale for the future use of lenvatinib in the treatment of ICC.

scholarly journals Naringenin Induces ROS-Mediated ER Stress, Autophagy, and Apoptosis in Human Osteosarcoma Cell Lines

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 373
Author(s):  
Chiang-Wen Lee ◽  
Cathy Chia-Yu Huang ◽  
Miao-Ching Chi ◽  
Kuan-Han Lee ◽  
Kuo-Ti Peng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Er Stress ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cyclin B1 ◽  
Cell Counting ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Cycle Arrest

Osteosarcoma, a primary bone tumor, responds poorly to chemotherapy and radiation therapy in children and young adults; hence, as the basis for an alternative treatment, this study investigated the cytotoxic and antiproliferative effects of naringenin on osteosarcoma cell lines, HOS and U2OS, by using cell counting kit-8 and colony formation assays. DNA fragmentation and the increase in the G2/M phase in HOS and U2OS cells upon treatment with various naringenin concentrations were determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and Annexin V/propidium iodide double staining, respectively. Flow cytometry was performed, and 2′,7′-dichlorodihydrofluorescein diacetate, JC-1, and Fluo-4 AM ester probes were examined for reactive oxygen species (ROS) generation, mitochondrial membrane potential, and intracellular calcium levels, respectively. Caspase activation, cell cycle, cytosolic and mitochondrial, and autophagy-related proteins were determined using with western blotting. The results indicated that naringenin significantly inhibited the viability and proliferation of osteosarcoma cells in a dose-dependent manner. In addition, naringenin induced cell cycle arrest in osteosarcoma cells by inhibiting cyclin B1 and cyclin-dependent kinase 1 expression and upregulating p21 expression. Furthermore, naringenin significantly inhibited the growth of osteosarcoma cells by increasing the intracellular ROS level. Naringenin induced endoplasmic reticulum (ER) stress-mediated apoptosis through the upregulation of ER stress markers, GRP78 and GRP94. Naringenin caused acidic vesicular organelle formation and increased autophagolysosomes, microtubule-associated protein-light chain 3-II protein levels, and autophagy. The findings suggest that the induction of cell apoptosis, cell cycle arrest, and autophagy by naringenin through mitochondrial dysfunction, ROS production, and ER stress signaling pathways contribute to the antiproliferative effect of naringenin on osteosarcoma cells.

scholarly journals Apoptosis Induction, Cell Cycle Arrest and in Vitro Anticancer Activity of Gonothalamin in a Cancer Cell Lines

2012 ◽  
Vol 13 (10) ◽  
pp. 5131-5136 ◽  
Author(s):  
Aied M. Alabsi ◽  
Rola Ali ◽  
Abdul Manaf Ali ◽  
Sami Abdo Radman Al-Dubai ◽  
Hazlan Harun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Apoptosis Induction ◽  
Cycle Arrest

Oleiferasaponin C6 from the seeds of Camellia oleifera Abel.: a novel compound inhibits proliferation through inducing cell-cycle arrest and apoptosis on human cancer cell lines in vitro

RSC Advances ◽  
2016 ◽  
Vol 6 (94) ◽  
pp. 91386-91393 ◽  
Author(s):  
Jianfa Zong ◽  
Dongxu Wang ◽  
Weiting Jiao ◽  
Liang Zhang ◽  
Guanhu Bao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Camellia Oleifera ◽  
Human Cancer Cell Lines ◽  
Cycle Arrest

Oleiferasaponin C6 was isolated from Camellia oleifera Abel. and inhibits proliferation through inducing cell-cycle arrest and apoptosis on cancer cell lines in vitro.

scholarly journals Menadione reduces CDC25B expression and promotes tumor shrinkage in gastric cancer

2020 ◽  
Vol 13 ◽  
pp. 175628481989543
Author(s):  
Amanda Braga Bona ◽  
Danielle Queiroz Calcagno ◽  
Helem Ferreira Ribeiro ◽  
José Augusto Pereira Carneiro Muniz ◽  
Giovanny Rebouças Pinto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Specific Inhibitor ◽  
Gastric Carcinogenesis ◽  
In Vivo Experiments ◽  
Cycle Arrest

Background: Gastric cancer is one of the most incident types of cancer worldwide and presents high mortality rates and poor prognosis. MYC oncogene overexpression is a key event in gastric carcinogenesis and it is known that its protein positively regulates CDC25B expression which, in turn, plays an essential role in the cell division cycle progression. Menadione is a synthetic form of vitamin K that acts as a specific inhibitor of the CDC25 family of phosphatases. Methods: To better understand the menadione mechanism of action in gastric cancer, we evaluated its molecular and cellular effects in cell lines and in Sapajus apella, nonhuman primates from the new world which had gastric carcinogenesis induced by N-Methyl-N-nitrosourea. We tested CDC25B expression by western blot and RT-qPCR. In-vitro assays include proliferation, migration, invasion and flow cytometry to analyze cell cycle arrest. In in-vivo experiments, in addition to the expression analyses, we followed the preneoplastic lesions and the tumor progression by ultrasonography, endoscopy, biopsies, histopathology and immunohistochemistry. Results: Our tests demonstrated menadione reducing CDC25B expression in vivo and in vitro. It was able to reduce migration, invasion and proliferation rates, and induce cell cycle arrest in gastric cancer cell lines. Moreover, our in-vivo experiments demonstrated menadione inhibiting tumor development and progression. Conclusions: We suggest this compound may be an important ally of chemotherapeutics in the treatment of gastric cancer. In addition, CDC25B has proven to be an effective target for investigation and development of new therapeutic strategies for this malignancy.

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