scholarly journals NFE2L3 Inhibition Induces Cell Cycle Arrest at the G0/G1 Phase in Colorectal Cancer Cells through Downregulating CCND1 and pRb1-ser807/811

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Lihua Zhang ◽  
Dong-Li Hu ◽  
Baiyou Tang ◽  
Yu Cheng ◽  
Chuan Jiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Sw480 Cell ◽  
G1 Phase ◽  
Tissue Samples ◽  
Expression Levels ◽  
Paired Samples ◽  
Cycle Arrest

The molecular mechanism for colorectal cancer to develop remains unelucidated. To find biomarkers related to colorectal cancer development, we analyzed the gene expression profile of 380 colorectal cancer patients and 51 healthy controls by R software. Finally, 1579 upregulated differential expression genes (DEGs) and 3218 downregulated DEGs were identified. Then, the top 20 upregulated DEGs were compared with 181 upregulated DEGs that we reported previously, and 11 overlapped DEGs were found. NFE2L3 (nuclear factor, erythroid 2-like 3) was among those overlapped DEGs and was rarely reported in colorectal cancer. Real-time polymerase chain reaction (PCR) results showed that higher NFE2L3 expression levels were identified in paired tumor samples than in paratumor samples (48 paired samples). Flow cytometry analysis revealed that the cell cycle was arrested at the G0/G1 phase after inhibition of NFE2L3 in both HCT116 and SW480 cell lines. Western blot detection showed that CCND1 and phosphorylated Rb transcriptional corepressor 1 at ser-807/811 (pRb1-ser807/811) expression levels were downregulated when NFE2L3 was inhibited in those two cell lines. A significant positive correlation was observed between NFE2L3 and CCND1 expression levels in colorectal tissue samples. These evidences indicate that downregulation of NFE2L3 induces cell cycle arrest at the G0/G1 phase through downregulation of CCND1 and pRb1-ser807/811.

scholarly journals Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 302 ◽  
Author(s):  
Xin Zhang ◽  
Yao Qin ◽  
Zhaohai Pan ◽  
Minjing Li ◽  
Xiaona Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cell Cycle Arrest ◽  
Phase Cell ◽  
G1 Phase ◽  
Therapeutic Effects ◽  
Human Gastric Cancer ◽  
Expression Levels ◽  
Cycle Arrest

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

scholarly journals Jianpi Huayu Decoction Inhibits Proliferation in Human Colorectal Cancer Cells (SW480) by Inducing G0/G1-Phase Cell Cycle Arrest and Apoptosis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Song-yang Xi ◽  
Yu-hao Teng ◽  
Yan Chen ◽  
Jie-ping Li ◽  
Ying-ying Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Caspase 3 ◽  
Cyclin D3 ◽  
Phase Cell ◽  
G1 Phase ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Sw480 Cells

Jianpi Huayu Decoction (JHD), a Chinese medicine formula, is a typical prescription against multiple tumors in the clinical treatment, which can raise quality of life and decrease complications. The aim of this study is to assess the efficacy of JHD against human colorectal carcinoma cells (SW480) and explore its mechanism. MTT assay showed that JHD decreased the cellular viability of SW480 cells in dose-dependent and time-dependent manner. Flow cytometry analysis revealed that JHD induced G0/G1-phase cell cycle arrest in SW480 cells and had a strong apoptosis-inducing effect on SW480 cells. Meanwhile it enhanced the expression of p27, cleaved PARP, cleaved caspase-3, and Bax and decreased the levels of PARP, caspase-3, Bcl-2, CDK2, CDK4, CDK6, cyclin D1, cyclin D2, cyclin D3, and cyclin E1, which was evidenced by RT-qPCR and Western blot analysis. In conclusion, these results indicated that JHD inhibited proliferation in SW480 cells by inducing G0/G1-phase cell cycle arrest and apoptosis, providing a practicaltherapeutic strategy against colorectal cancer.

scholarly journals Peptide SA12 inhibits proliferation of breast cancer cell lines MCF-7 and MDA-MB-231 through G0/G1 phase cell-cycle arrest

2018 ◽  
Vol Volume 11 ◽  
pp. 2409-2417 ◽  
Author(s):  
Longfei Yang ◽  
Huanran Liu ◽  
Min Long ◽  
Xi Wang ◽  
Fang Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Phase Cell ◽  
G1 Phase ◽  
Breast Cancer Cell Lines ◽  
Cycle Arrest ◽  
Mcf 7

scholarly journals Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1295
Author(s):  
Guoli Li ◽  
Sining Fang ◽  
Xiao Shao ◽  
Yejia Li ◽  
Qingchao Tong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Induced Resistance ◽  
Phase Cell ◽  
Ros Generation ◽  
Antitumor Effects ◽  
Cycle Arrest

Nicotinamide N-methyltransferase (NNMT) plays multiple roles in improving the aggressiveness of colorectal cancer (CRC) and enhancing resistance to 5-Fluorouracil (5-FU), making it an attractive therapeutic target. Curcumin (Cur) is a promising natural compound, exhibiting multiple antitumor effects and potentiating the effect of 5-FU. The aim of the present study is to explore the effect of Cur on attenuating NNMT-induced resistance to 5-FU in CRC. A panel of CRC cell lines with different NNMT expressions are used to characterize the effect of Cur. Herein, it is observed that Cur can depress the expression of NNMT and p-STAT3 in CRC cells. Furthermore, Cur can induce inhibition of cell proliferation, G2/M phase cell cycle arrest, and reactive oxygen species (ROS) generation, especially in high-NNMT-expression CRC cell lines. Cur can also re-sensitize high-NNMT-expression CRC cells to 5-FU both in vitro and in vivo. In summary, it is proposed that Cur can reverse NNMT-induced cell proliferation and 5-FU resistance through ROS generation and cell cycle arrest. Given that Cur has long been used, we suppose that Cur is a promising anticancer drug candidate with minimal side effects for human CRC therapy and can attenuate NNMT-induced resistance to 5-FU.

The effects of licofelone, a dual lipoxygenase and cyclooxygenase inhibitor, with and without rosiglitazone in human MCF-7 and MDA-MB-231 breast cancer cells

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1537-1537 ◽  
Author(s):  
C. Kurkjian ◽  
N. B. Janakiram ◽  
S. Guruswamy ◽  
C. V. Rao ◽  
H. Ozer
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Combination Therapy ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Low Dose ◽  
G1 Phase ◽  
Cycle Arrest ◽  
Dose Combination ◽  
Mcf 7

1537 Background: Clinical and preclinical studies suggest that cyclooxygenase (COX)-2 inhibitors reduce the risk of various cancers, however, their administration is associated with an increased cardiovascular risk. Agents with 5-LOX/COX inhibition provide a possible approach for improving chemopreventive efficacy without unwanted side effects. COX and LOX inhibition have also been associated with an increase in PPAR γ expression. The present experiments tested the effects of licofelone (L) in breast cancer cell lines and assessed whether dual inhibition of LOX and COX may potentiate the action of rosiglitazone (R). Methods: MDA-MB-231 and MCF-7 cells were exposed to sub-toxic concentrations of L and R alone and in combination and analyzed for growth inhibition (MTT method), apoptosis (EB-AO and DAPI methods), cell-cycle analysis (flow cytometry), and protein expression (immunoblot method). Results: L and R inhibited cell growth in a dose-dependent manner in both cell lines. Combination therapy resulted in significant rates of apoptosis, particularly at high doses in both cell lines (p<0.001). Flow cytometric analysis showed that L and R exhibited cell cycle arrest at the G0/G1 phase in MDA-MB-231 cells. The low dose combination did not promote cell cycle arrest while the higher dose combination therapy demonstrated significant inhibition (p <0.0009). In MCF-7 cells, G0/G1 phase blockade was noted in L and R treated cells as well as in the low dose simultaneous combination therapy. Intermediate and high dose combination therapy exhibited increased cell cycle arrest at G0/G1 when L was administered 12 hours before R (p = 0.0030 and 0.0017). Western blot analysis showed increased expression of p21WAFI/CIPI and decreased cyclin D1 expression in both cell lines after therapy. Both agents induced caspase-3 expression in MDA-MB-231 cells at high concentrations, with even higher expression observed in the combination treatment. MCF-7 cells demonstrated PARP cleavage at all doses when compared to control. Conclusions: Our results suggest that L is a potential agent for prevention and treatment of breast cancer and the combination of low doses of L and R provide further promise in improving efficacy against breast cancer. No significant financial relationships to disclose.

The mTOR Inhibitor Temsirolimus (CCI-779) Induces Cell Cycle Arrest and Autophagy in Hodgkin Lymphoma (HL) Cell Lines and Enhances the Effect of the PI3-Kinase Inhibitor LY294002.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2259-2259 ◽  
Author(s):  
Georgios V. Georgakis ◽  
Victor Y. Yazbeck ◽  
Yang Li ◽  
Anas Younes
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Mtor Inhibitor ◽  
Kinase Inhibitor ◽  
G1 Phase ◽  
Clinical Activity ◽  
Cell Cycle Protein ◽  
Acridine Orange Staining ◽  
Cycle Arrest

Abstract The PI3K/AKT/mTOR pathway is frequently activated in a variety of cancers giving hope that that this pathway may prove to be a good target for cancer therapy. We and others have recently reported that primary and cultured Hodgkin and Reed-Sternberg cells of HL express the active phosphorylated form of Akt (pAkt) which contribute to their survival. Furthermore, we have demonstrated that inhibition of PI3K by the small molecule LY294002 or Akt inhibition induced cell cycle arrest and apoptosis. However, at the present time there is no PI3K or Akt inhibitors in clinical trials. Instead, several inhibitors of the downstream mTOR kinase are already being evaluated in patients with cancer. Temsirolimus (CCI-779) is an mTOR inhibitor that demonstrated promising clinical activity in patients with relapsed mantle cell lymphoma. To explore the potential clinical activity of Temsirolimus in HL, we examined its efficacy in HL-derived cell lines (HD-LM2, L-428, and KM-H2). Here, we demonstrate that CCI-779 inhibited mTOR, as evident by the inhibition of ribosomal S6 phosphorylation as early as 6 hours, with a dose as low as 1 nM. Temsirolimus induced antiproliferative cytostatic effect in the same dose (1nM) in all HL cell lines, and this effect did not improve with higher concentrations (up to 1000 nM). Furthermore, the effect was predominantly cytostatic with little or no induction of apoptosis. This antiproliferative effect was predominantly due to cell cycle arrest in G0/G1 phase, and was associated with upregulation of p27 cell cycle protein. Although temsirolimus did not induce apoptosis, it induced autophagy, as determined by Acridine Orange staining of the acidic autophagic intracellular organelles and FACS analysis. Combination of 1nM CCI-779 with increasing concentrations of the PI3K inhibitor LY294002 showed a profound decrease in the IC50 of LY294002 in all 3 cell lines. Moreover, the combination of CCI-779 and LY294002 blocked cell cycle at G0/G1 phase more efficiently and significantly increased autophagic cells when compared with each agent alone, but failed to induce apoptosis. This effect was mediated in part by inhibiting a negative feedback loop involving AKT phosphorylation. Collectively, our data suggest that temsirolimus may have a therapeutic value in HL.

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