scholarly journals Hsa‑miR‑376c‑3p targets Cyclin D1 and induces G1‑cell cycle arrest in neuroblastoma cells

2018 ◽  
Author(s):  
Swapnil Bhavsar ◽  
Cecilie L�kke ◽  
Trond Fl�gstad ◽  
Christer Einvik
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Neuroblastoma Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

scholarly journals Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells

Oncogene ◽  
2005 ◽  
Vol 24 (36) ◽  
pp. 5606-5618 ◽  
Author(s):  
Christopher J Wallick ◽  
Ivonne Gamper ◽  
Mike Thorne ◽  
David J Feith ◽  
Kelsie Y Takasaki ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Neuroblastoma Cells ◽  
Retinoblastoma Protein ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

SF1126, a Pan-PI3K Inhibitor Has Superior Preclinical Activity to CAL-101 a PI3K Delta-Specific Inhibitor in Aggressive B-Cell Non-Hodgkin's Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2720-2720 ◽  
Author(s):  
Daruka Mahadevan ◽  
Wenqing Qi ◽  
Amy Stejskal ◽  
Laurence Cooke ◽  
Joseph R Garlich
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
B Cell ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Specific Inhibitor ◽  
Pi3k Pathway ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

Abstract Abstract 2720 The PI3K pathway is constitutively active in B-cell non-Hodgkin lymphomas (B-NHL). PI3K pathway targeted therapies have focused on inhibiting mTORC1 (rapalogs) with a ∼20–48% response rate due to inactivation of mTORC1 resulting in G1 cell-cycle arrest or apoptosis. A mechanism of resistance to rapalogs is that mTORC2 is unaffected resulting in undesirable Akt activation. Strategies to block Akt up-regulation require novel agents that simultaneously block PI3K, mTORC1 and mTORC2. SF1126 is a novel pan-PI3K/mTORC1/mTORC2 inhibitor conjugated to an integrin targeted peptide RGD with potent anti-tumor activity in multiple solid tumor types. Here, we demonstrated SF1126 had potent anti-B-NHL activity and is superior to CAL-101 a PI3K delta-isoform specific inhibitor in a panel of aggressive B-NHL cell lines. Cells treated with SF1126 exhibited >90% decrease in pAkt and pGSK-3β confirming the mechanism of action of a pan-PI3K inhibitor. Moreover, SF1126 induced apoptosis in a dose and time dependent manner confirmed by flow cytometry, PARP cleavage and with an IC50 < 4μM. In contrast, CAL-101 was less active compared to SF1126 in inducing apoptosis (12% versus 25% in SUDHL-4 and 15% versus 23% in TMD-8) and cell proliferation (5.62μM versus 3.28μM SUDHL-4 and 5.31μM versus 1.47μM in TMD-8). SF1126 induced G1 cell cycle arrest at 2μM which contributes to suppression of cell proliferation. The cell cycle protein cyclin D1 is downstream of mTORC1, and the over-expression of cyclin D1 is a hallmark of mantle cell NHL (MCL). Consistent with this, cyclin D1 was significantly decreased by SF1126 compared to CAL-101. Lastly, the addition of Rituximab to SF1126 or CAL101 increased the apoptosis over single agent therapy in B-NHL cell lines. In conclusion, we demonstrate that SF1126 potently inhibits the constitutively activated PI3K/mTORC/Akt pathway in aggressive B-cell NHL cell lines with consequent suppressive effects on cell cycle progression, cell proliferation and induction of apoptosis. These findings provide a rationale for SF1126 in combination with rituximab as a novel therapeutic strategy for aggressive B-NHL and warrant early phase clinical trial evaluation [Funded by the Lymphoma SPORE 1 P50 CA 130805 01A1]. Disclosures: Garlich: Semafore Pharmaceuticals: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

scholarly journals SOX7 is involved in polyphyllin D-induced G0/G1 cell cycle arrest through down-regulation of cyclin D1

2020 ◽  
Vol 70 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Bin Zheng ◽  
Gang Wang ◽  
Wenbo Gao ◽  
Qiquan Wu ◽  
Weizhi Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Complete Medium ◽  
Dependent Manner ◽  
Cyclin Dependent Kinase ◽  
Down Regulation ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Polyphyllin D

AbstractThe incidence of mortality of prostate cancer (PCa) has been an uptrend in recent years. Our previous study showed that the sex-determining region Y-box 7 (SOX7) was low-expressed and served as a tumor suppressor in PCa cells. Here, we describe the effects of polyphyllin D (PD) on proliferation and cell cycle modifications of PCa cells, and whether SOX7 participates in this process. PC-3 cells were cultured in complete medium containing PD for 12, 24, and 48 h. MTT assay was used to investigate the cytotoxic effects of PD. Cell cycle progression was analyzed using propidium iodide (PI) staining, and protein levels were assayed by Western blot analysis. Our results showed low expression of SOX7 in PCa tissues/cells compared to their non-tumorous counterparts/RWPE-1 cells. Moreover, PD inhibited the proliferation of PC-3 cells in a dose- and time-dependent manner. PD induced G0/G1 cell cycle arrest, while co-treatment with short interfering RNA targeting SOX7 (siSOX7) had reversed this effect. PD downregulated SOX7, cyclin D1, cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) expressions in a dose-dependent manner, whereas co-treatment of siSOX7 and PD rescued the PD-inhibited cyclin D1 expression. However, no obvious changes were observed in CDK4 or CDK6 expression. These results indicate that SOX7 is involved in PD-induced PC-3 cell cycle arrest through down-regulation of cyclin D1.

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