scholarly journals RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1244
Author(s):  
Min Yu ◽  
Xiaoyan Hu ◽  
Jingyu Yan ◽  
Ying Wang ◽  
Fei Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Cyclin E ◽  
Intraperitoneal Administration ◽  
Glioblastoma Cells ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
P53 Signaling Pathway

Up to now, the chemotherapy approaches for glioblastoma were limited. 1-[2-Thiazolylazo]-2-naphthol (named as NSC139021) was shown to significantly inhibit the proliferation of prostate cancer cells by targeting the atypical protein kinase RIOK2. It is documented that RIOK2 overexpressed in glioblastoma. However, whether NSC139021 can inhibit the growth of glioblastoma cells and be a potential drug for glioblastoma treatment need to be clarified. In this study, we investigated the effects of NSC139021 on human U118MG, LN-18, and mouse GL261 glioblastoma cells and the mouse models of glioblastoma. We verified that NSC139021 effectively inhibited glioblastoma cells proliferation, but it is independent of RIOK2. Our data showed that NSC139021 induced cell cycle arrest at G0/G1 phase via the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway in G1/S checkpoint regulation. In addition, NSC139021 also increased the apoptosis of glioblastoma cells by activating the p53 signaling pathway and increasing the levels of Bax and cleaved caspase 3. Furthermore, intraperitoneal administration of 150 mg/kg NSC139021 significantly suppressed the growth of human and mouse glioblastoma in vivo. Our study suggests that NSC139021 may be a potential chemotherapy drug for the treatment of glioblastoma by targeting the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway.

scholarly journals Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

2016 ◽  
Vol 12 (6) ◽  
pp. 4605-4612 ◽  
Author(s):  
Ping Wang ◽  
Jiayue Cui ◽  
Jihong Wen ◽  
Yunhui Guo ◽  
Liangzi Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Hepg2 Cell ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
P53 Signaling Pathway

scholarly journals DREAM and RB cooperate to induce gene repression and cell-cycle arrest in response to p53 activation

2019 ◽  
Vol 47 (17) ◽  
pp. 9087-9103 ◽  
Author(s):  
Sigrid Uxa ◽  
Stephan H Bernhart ◽  
Christina F S Mages ◽  
Martin Fischer ◽  
Robin Kohler ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Genotoxic Stress ◽  
Gene Repression ◽  
Pocket Proteins ◽  
Cell Cycle Genes ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
P53 Signaling Pathway

Abstract Most human cancers acquire mutations causing defects in the p53 signaling pathway. The tumor suppressor p53 becomes activated in response to genotoxic stress and is essential for arresting the cell cycle to facilitate DNA repair or to initiate apoptosis. p53-induced cell cycle-arrest is mediated by expression of the CDK inhibitor p21WAF1/Cip1, which prevents phosphorylation and inactivation of the pocket proteins RB, p130, and p107. In a hypophosphorylated state, pocket proteins bind to E2F factors forming RB-E2F and DREAM transcriptional repressor complexes. Here, we analyze the influence of RB and DREAM on p53-induced gene repression and cell-cycle arrest. We show that abrogation of DREAM function by knockout of the DREAM component LIN37 results in a reduced repression of cell-cycle genes. We identify the genes repressed by the p53-DREAM pathway and describe a set of genes that is downregulated by p53 independent of LIN37/DREAM. Most strikingly, p53-dependent repression of cell-cycle genes is completely abrogated in LIN37−/−;RB−/− cells leading to a loss of the G1/S checkpoint. Taken together, we show that DREAM and RB are key factors in the p53 signaling pathway to downregulate a large number of cell-cycle genes and to arrest the cell cycle at the G1/S transition.

scholarly journals Bisphenol A induces cell cycle arrest in primary and prostate cancer cells through EGFR/ERK/p53 signaling pathway activation

Oncotarget ◽  
2017 ◽  
Vol 8 (70) ◽  
pp. 115620-115631 ◽  
Author(s):  
Antonio Bilancio ◽  
Paola Bontempo ◽  
Marzia Di Donato ◽  
Mariarosaria Conte ◽  
Pia Giovannelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Bisphenol A ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
Pathway Activation ◽  
P53 Signaling Pathway

scholarly journals Standardized Saponin Extract from Baiye No.1 Tea (Camellia sinensis) Flowers Induced S Phase Cell Cycle Arrest and Apoptosis via AKT-MDM2-p53 Signaling Pathway in Ovarian Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3515
Author(s):  
Youying Tu ◽  
Lianfu Chen ◽  
Ning Ren ◽  
Bo Li ◽  
Yuanyuan Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Camellia Sinensis ◽  
High Purity ◽  
S Phase ◽  
Phase Cell ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
P53 Signaling Pathway

Ovarian cancer is considered to be one of the most serious malignant tumors in women. Natural compounds have been considered as important sources in the search for new anti-cancer agents. Saponins are characteristic components of tea (Camellia sinensis) flower and have various biological activities, including anti-tumor effects. In this study, a high purity standardized saponin extract, namely Baiye No.1 tea flower saponin (BTFS), which contained Floratheasaponin A and Floratheasaponin D, were isolated from tea (Camellia sinensis cv. Baiye 1) flowers by macroporous resin and preparative liquid chromatography. Then, the component and purity were detected by UPLC-Q-TOF/MS/MS. This high purity BTFS inhibited the proliferation of A2780/CP70 cancer cells dose-dependently, which is evidenced by the inhibition of cell viability, reduction of colony formation ability, and suppression of PCNA protein expression. Further research found BTFS induced S phase cell cycle arrest by up-regulating p21 proteins expression and down-regulating Cyclin A2, CDK2, and Cdc25A protein expression. Furthermore, BTFS caused DNA damage and activated the ATM-Chk2 signaling pathway to block cell cycle progression. Moreover, BTFS trigged both extrinsic and intrinsic apoptosis—BTFS up-regulated the expression of death receptor pathway-related proteins DR5, Fas, and FADD and increased the ratio of pro-apoptotic/anti-apoptotic proteins of the Bcl-2 family. BTFS-induced apoptosis seems to be related to the AKT-MDM2-p53 signaling pathway. In summary, our results demonstrate that BTFS has the potential to be used as a nutraceutical for the prevention and treatment of ovarian cancer.

scholarly journals Effect of Radix Hedysari Polysaccharide on Glioma by Cell Cycle Arrest and TNF-α Signaling Pathway Regulation

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Xiaolong Du ◽  
Yujing Zhao ◽  
Yongqian Ma ◽  
Hongshun Xing ◽  
Xingang Li
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Signaling Pathway ◽  
Nude Mice ◽  
U251 Cell ◽  
Cycle Arrest ◽  
U251 Cells

Objective. To investigate the possible development of radix hedysari polysaccharide as an antiglioma drug, we studied the effect of radix hedysari polysaccharide on glioma cells in vitro and the growth of glioma in nude mice and on the phagocytosis of macrophages in nude mice with glioma. Methods. The effect of radix hedysari polysaccharide on the growth of glioma was studied based on U251 cell line in vitro. The effect of radix hedysari polysaccharide on the growth of glioma was studied in vivo. The growth inhibition rate of radix hedysari polysaccharide on U251 cell line was determined by the MTT assay. The cell cycle of U251 was analyzed by flow cytometry. The expression of cytokines in U251 cells and tumor tissues was detected using PCR. The phagocytosis of macrophages in the serum of glioma nude mice was detected by Giemsa staining. TNF-α signaling pathway proteins in the serum of glioma nude mice were detected by ELISA. Results. Radix hedysari polysaccharide inhibited the growth of U251 cells, induced apoptosis in G1 phase by cell cycle arrest, and facilitated apoptosis in glioma mice by regulating cell cycle. Mice injected with radix hedysari polysaccharide showed delayed tumor growth and grew slowly. Radix hedysari polysaccharide enhanced the phagocytosis of macrophages in glioma nude mice. Radix hedysari polysaccharides could inhibit tumor development by regulating the immune function of tumor mice and affecting the TNF-α signaling pathway. Conclusion. Radix hedysari polysaccharide can effectively inhibit the growth of glioma and affect the TNF-α signaling pathway, thus playing an antiglioma role.

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