scholarly journals Novel chemotherapeutic agent FX-9 activates NF-κB signaling and induces G1 phase arrest by activating CDKN1A in a human prostate cancer cell line

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
F. Weiner ◽  
J. T. Schille ◽  
D. Koczan ◽  
X.-F. Wu ◽  
M. Beller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Inflammatory Response ◽  
Expression Analysis ◽  
Secondary Response ◽  
G1 Phase ◽  
Cell Cycle Inhibitor ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Pai 1

Abstract Background The aminoisoquinoline FX-9 shows pro-apoptotic and antimitotic effects against lymphoblastic leukemia cells and prostate adenocarcinoma cells. In contrast, decreased cytotoxic effects against non-neoplastic blood cells, chondrocytes, and fibroblasts were observed. However, the actual FX-9 molecular mode of action is currently not fully understood. Methods In this study, microarray gene expression analysis comparing FX-9 exposed and unexposed prostate cancer cells (PC-3 representing castration-resistant prostate cancer), followed by pathway analysis and gene annotation to functional processes were performed. Immunocytochemistry staining was performed with selected targets. Results Expression analysis revealed 0.83% of 21,448 differential expressed genes (DEGs) after 6-h exposure of FX-9 and 0.68% DEGs after 12-h exposure thereof. Functional annotation showed that FX-9 primarily caused an activation of inflammatory response by non-canonical nuclear factor-kappa B (NF-κB) signaling. The 6-h samples showed activation of the cell cycle inhibitor CDKN1A which might be involved in the secondary response in 12-h samples. This secondary response predominantly consisted of cell cycle-related changes, with further activation of CDKN1A and inhibition of the transcription factor E2F1, including downstream target genes, resulting in G1-phase arrest. Matching our previous observations on cellular level senescence signaling pathways were also found enriched. To verify these results immunocytochemical staining of p21 Waf1/Cip1 (CDKN1A), E2F1 (E2F1), PAI-1 (SERPNE1), and NFkB2/NFkB p 100 (NFKB2) was performed. Increased expression of p21 Waf1/Cip1 and NFkB2/NFkB p 100 after 24-h exposure to FX-9 was shown. E2F1 and PAI-1 showed no increased expression. Conclusions FX-9 induced G1-phase arrest of PC-3 cells through activation of the cell cycle inhibitor CDKN1A, which was initiated by an inflammatory response of noncanonical NF-κB signaling.

scholarly journals Hepatitis B virus induces G1 phase arrest by regulating cell cycle genes in HepG2.2.15 cells

2011 ◽  
Vol 8 (1) ◽  
pp. 231 ◽  
Author(s):  
Tianzhen Wang ◽  
Ran Zhao ◽  
Yiqi Wu ◽  
Dan Kong ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
G1 Phase ◽  
Cell Cycle Genes ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
B Virus

scholarly journals CCNE1 and E2F1 Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment

2021 ◽  
Vol 22 (21) ◽  
pp. 11623
Author(s):  
Kei Kikuchi ◽  
Daisuke Kaida
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
G1 Phase ◽  
Cell Cycle Regulators ◽  
Protein Levels ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Spliceostatin A

The potent splicing inhibitor spliceostatin A (SSA) inhibits cell cycle progression at the G1 and G2/M phases. We previously reported that upregulation of the p27 cyclin-dependent kinase inhibitor encoded by CDKN1B and its C-terminal truncated form, namely p27*, which is translated from CDKN1B pre-mRNA, is one of the causes of G1 phase arrest caused by SSA treatment. However, the detailed molecular mechanism underlying G1 phase arrest caused by SSA treatment remains to be elucidated. In this study, we found that SSA treatment caused the downregulation of cell cycle regulators, including CCNE1, CCNE2, and E2F1, at both the mRNA and protein levels. We also found that transcription elongation of the genes was deficient in SSA-treated cells. The overexpression of CCNE1 and E2F1 in combination with CDKN1B knockout partially suppressed G1 phase arrest caused by SSA treatment. These results suggest that the downregulation of CCNE1 and E2F1 contribute to the G1 phase arrest induced by SSA treatment, although they do not exclude the involvement of other factors in SSA-induced G1 phase arrest.

scholarly journals ESRP1 Induces Cervical Cancer Cell G1-Phase Arrest Via Regulating Cyclin A2 mRNA Stability

2019 ◽  
Vol 20 (15) ◽  
pp. 3705 ◽  
Author(s):  
Zhi-Hong Chen ◽  
Ya-Jie Jing ◽  
Jian-Bo Yu ◽  
Zai-Shu Jin ◽  
Zhu Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Cyclin A2 ◽  
The Stability

Accumulating evidence indicates that epithelial splicing regulatory protein 1 (ESRP1) can inhibit the epithelial-to-mesenchymal transition (EMT), thus playing a central role in regulating the metastatic progression of tumors. However, it is still not clear whether ESRP1 directly influences the cell cycle, or what the possible underlying molecular mechanisms are. In this study, we showed that ESRP1 protein levels were significantly correlated with the Ki-67 proliferative index (r = −0.521; p < 0.01), and that ESRP1 overexpression can significantly inhibit cervical carcinoma cell proliferation and induced G1-phase arrest by downregulating cyclin A2 expression. Importantly, ESRP1 can bind to GGUGGU sequence in the 3′UTR of the cyclin A2 mRNA, and ESRP1 overexpression significantly decreases the stability of the cyclin A2 mRNA. In addition, our experimental results confirm that ESRP1 overexpression results in enhanced CDC20 expression, which is known to be responsible for cyclin A2 degradation. This study provides the first evidence that ESRP1 overexpression induces G1-phase cell cycle arrest via reducing the stability of the cyclin A2 mRNA, and inhibits cervical carcinoma cell proliferation. The findings suggest that the ESRP1/cyclin A2 regulatory axis may be essential as a regulator of cell proliferation, and may thus represent an attractive target for cervical cancer prevention and treatment.

scholarly journals 6-Gingerol induces cell-cycle G1-phase arrest through AKT–GSK 3β–cyclin D1 pathway in renal-cell carcinoma

2019 ◽  
Vol 85 (2) ◽  
pp. 379-390
Author(s):  
Shan Xu ◽  
Haibao Zhang ◽  
Tianjie Liu ◽  
Wenjie Yang ◽  
Wei Lv ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cyclin D1 ◽  
Renal Cell ◽  
Colony Formation ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Gsk 3Β

Abstract Purpose 6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary. Methods The effects of 6-gingerol on proliferation, colony formation, and cell cycle in RCC cells were detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and propidium iodide (PI) staining, respectively. Western blotting, an immunofluorescence assay, and immunohistochemical staining were performed to assess the expression of relevant proteins. A subcutaneous tumor model was set up to investigate the 6-gingerol effects on tumor growth in vivo, and the pharmacokinetics of 6-gingerol in mice were detected by LC/MS assays. Results 6-Gingerol treatment exerted time- and dose-dependent inhibition of the growth and colony formation of ACHN, 786-O, and 769-P cells, leading to a concomitant induction of cell-cycle G1-phase arrest and decrease in Ki-67 expression in the cell nucleus. Western-blotting results showed that 6-gingerol reduces phosphorylation of protein kinase B (AKT) Ser 473, cyclin-dependent kinases (CDK4), and cyclin D1 and, meanwhile, increases glycogen synthase kinase (GSK 3β) protein amount. Furthermore, the efficacy of 6-gingerol was demonstrated in an in vivo murine model of 786-O. Conclusion The above results indicate that 6-gingerol can induce cell-cycle arrest and cell-growth inhibition through the AKT–GSK 3β–cyclin D1 signaling pathway in vitro and in vivo, suggesting that 6-gingerol should be useful for renal-cell carcinoma treatment.

Oroxylin A Induce Differentiation and G0/G1 Phase Arrest of Acute Myeloid Leukemia (AML)Cells Via Effects on PPARγ/RXRα Heterodimers,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3635-3635
Author(s):  
Hui Hui ◽  
Bao-An Chen ◽  
Qing-long Guo
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Nuclear Receptor ◽  
G1 Phase ◽  
U937 Cells ◽  
Monocytic Differentiation ◽  
Oroxylin A ◽  
Inhibition Effect ◽  
Phase Arrest ◽  
G1 Phase Arrest

Abstract Abstract 3635 Objective: It has been shown that oroxylin A, a monoflavonoid extracted from the root of the Chinese herb medicine Scutellaria baicalensis, could effectively inhibit the proliferation of several cancer cell lines. However, little is known about the effect of oroxylin A on leukemic cells. In the current study the effects of oroxylin A were analized on growth, differentiation and cell cycle of myeloid leukemic cell lines. Methods: This study used AML cell lines including NB4, U937 and HL60. Expression and distribution of the proteins were analyzed by flow cytometry, western blots and Immunofluoresence assay. The growth inhibition effect of the drug was evaluated by MTT and cell cycle assay. The differentiation of cells was estimated by Giemsa stain and NBT reduction assay. Results: The growth of U937, HL60 and NB4 cells incubated with oroxylin A was inhibited in a time- and concentration-dependent manner but no apoptosis effect could be observed. Moreover, oroxylin A induced monocytic differentiation and G0/G1 phase arrest in U937 and HL60 cells, meanwhile, the expresstion of PPARγ, a nuclear receptor correlated with monocytic differentiation, was enhanced specificly and a nuclear accumulation of PPARγ was induced. Effects of differentiation and the upregulation of p21 could be attenuated by GW9662, a specific inhibitor of PPARγ. Oroxylin A dramatically displayed synergistic effect with ATRA or VD3 on growth and differentiation of NB4 or U937 cells respectively. We investigated the phosphorylation of RXRα, a nuclear receptor which assists RARα, PPARγ and VDR to exert differentiation effects through heterodimerize with them, was inhibited especially in nuclear of NB4, U937 and HL60 cells treated with oroxylin A. Activition of MAPK/ERK pathway, which is responsible for phosphorylation of RXRα, was also inhibited by oroxylin A. Conclusion: The results showed here demonstrated that oroxylin A could induce growth inhibition, G0/G1 phase arrest and differentiation of U937 and HL60 and show synergistic effects in combination with ATRA in NB4 and with VD3 in U937 cells via potential inhibition effect on phosphorylation of RXRα. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Histone deacetylase inhibitor BL1521 induces a G1-phase arrest in neuroblastoma cells through altered expression of cell cycle proteins

FEBS Letters ◽  
2005 ◽  
Vol 579 (6) ◽  
pp. 1523-1528 ◽  
Author(s):  
Krista Ouwehand ◽  
Annemieke J.M. de Ruijter ◽  
Chris van Bree ◽  
Huib N. Caron ◽  
André B.P. van Kuilenburg
Keyword(s):  
Cell Cycle ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Neuroblastoma Cells ◽  
G1 Phase ◽  
Cell Cycle Proteins ◽  
Altered Expression ◽  
Phase Arrest ◽  
Deacetylase Inhibitor ◽  
G1 Phase Arrest
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