Regenerating Gene 1B Silencing Inhibits Colon Cancer Cell HCT116 Proliferation and Invasion

2015 ◽  
Vol 30 (2) ◽  
pp. 217-225 ◽  
Author(s):  
Zhirong Liu ◽  
Yuehong Zhang ◽  
Jun Xie ◽  
Caiping Li ◽  
Xiaoxia Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Colorectal Carcinoma ◽  
Cell Cycle Arrest ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Cycle Arrest ◽  
Hct116 Cells

Background The human regenerating gene 1B ( REG1B) is found to be frequently up-regulated in many types of human tumors. It is unclear whether REG1B expression may have therapeutic value in colorectal carcinoma. Additionally, how REG1B is associated with the clinical features of colorectal carcinoma is not known. To investigate the relationship between REG1B and colorectal cancer, we analyzed REG1B expression in clinical specimens and cell lines and the effect of down-regulation of REG1B by short hairpin RNA (shRNA) in HCT116 cells. Methods Paraffin-embedded specimens from 30 pairs of colorectal cancer tissues and adjacent colon tissues were used to investigate the expression of REG1B by immunohistochemistry. We also examined whether REG1B itself may be related to cell proliferation, cell cycle arrest, apoptosis, migration and invasion in colon cancer HCT116 cells. Results Our results showed that REG1B was highly expressed in colorectal carcinoma and was significantly associated with cell differentiation status. The results also illustrated that REG1B silencing with shRNA inhibited cell proliferation, migration and invasion but did not induce apoptosis. Furthermore, down-regulation of REG1B induces G1-phase cell cycle arrest in colon cancer cells. Conclusions Knockdown of REG1B can inhibit cell proliferation, migration and invasion. It may act by a mechanism regulating cell cycle progression. Thus, REG1B may be a novel candidate therapeutic target for colorectal cancer.

scholarly journals Berberine and Evodiamine Synergically Exert Anti-colorectal Cancer Effeccts via P38/MAPK/MAPKAPK2/HSP27 Signaling Pathway

2022 ◽  
Author(s):  
Ningning Chen ◽  
Yifang Jiang ◽  
Yi Yang ◽  
Ziyi Zhao ◽  
Chong Xiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Natural Products ◽  
Cell Cycle Arrest ◽  
P38 Mapk ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Cycle Arrest

Abstract Objective: Combinatorial natural products have high application potential for treatment of complex diseases owing to their synergistic effects and multi-targeting effect. However, studies have not explored the therapeutic effect and the synergetic mechanisms of action combinations of natural products. The present study aimed sought to evaluate the synergistic antitumor effects of a combination of Berberine and Evodiamine, and explore the drug effect on proliferation, migration, invasion of HCT116 and RKO human colorectal cancer cells. Results: The effect of berberine and evodiamine at a specific paired dose (BER30μM, EVO 0.8μM) was explored. A combination of berberine and evodiamine had no effect on activity and proliferation of HCT116 and RKO cells. The combination regulates the cell cycle of HCT116 and RKO cells at different cell phases. Berberine mainly blocked the cell cycle at G0/G1 phase, whereas evodiamine induced cell cycle arrest at G2/M phase. The results showed that the combined effect of berberine and evodiamine does not offset each other, but plays a synergistic role in regulation of colon cancer cell cycle. Western blot analysis showed that the combination of berberine and evodiamine regulated cell cycle by downregulating expression of cdc25c and upregulating expression of p21. The combination significantly inhibited cell migration and invasion by regulating EMT related proteins, upregulating expression of E-cadherin and downregulating expression of N-cadherin. The combination of berberine and evodiamine significantly inhibited phosphorylation of P38 MAPK in HCT116 and RKO cells, and further inhibited phosphorylation of the downstream MAPKAPK2 and HSP27, thus playing a synergistic anti-colon cancer role.Conclusion: Berberine and Evodiamine exhibit synergistic antitumor effects by suppressing cell proliferation, inducing cell cycle arrest and inhibiting EMT by modulating P38MAPK /MAPKAPK2/HSP27 pathway.Significance of the study: To illustrate the potential mechanism of formula-based combination of natural products, and explore the potential applications of the combination and possible antitumor therapeutic targets.

scholarly journals Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1329 ◽  
Author(s):  
Kaluzki ◽  
Hailemariam-Jahn ◽  
Doll ◽  
Kaufmann ◽  
Balermpas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Colorectal Carcinoma ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Carcinoma Cell ◽  
Human Colon ◽  
G1 Phase ◽  
Cycle Arrest

Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct antitumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.

Celastrol inhibits the proliferation and induces apoptosis of colorectal cancer cells via downregulating NF-κB/COX-2 signaling pathways

2021 ◽  
Vol 21 ◽  
Author(s):  
Hua Zhang ◽  
Xiaojin Zhao ◽  
Fajun Shang ◽  
Huan Sun ◽  
Xu Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
The World ◽  
Cox 2

Background: Colorectal cancer (CRC) is the third-ranked malignant tumor in the world that contributes to the death of a major population of the world. Celastrol, a bioactive natural product isolated from the medicinal plant Tripterygium wilfordii Hook F, has been proved to be an effective anti-tumor inhibitor for multiple tumors. Objective: To reveal the therapeutic effect and underlying mechanisms of celastrol on CRC cells. Methods: CCK-8 and clonogenic assay were used to analyze the cell proliferation in CRC cells. Flow cytometry analysis was conducted to assess the cell cycle and cell apoptosis. Wound-healing and cell invasion assay were used to evaluate the migrating and invasion capability of CRC cells. The potential antitumor mechanism of celastrol was investigated by qPCR, western blot, and confocal immunofluorescence analyses. Results: Celastrol effectively inhibited CRC cell proliferation by activating caspase-dependent cell apoptosis and facilitating G1 cell cycle arrest in a dose-dependent manner, as well as cell migration and invasion by downregulating the MMP2 and MMP9. Mechanistic protein expression revealed that celastrol suppressed the expression of COX-2 by inhibiting the phosphorylation of NF-κB p65 and subsequently leading to cytoplasmic retention of p65 protein, thereby inhibiting its nuclear translocation and transcription activities. Conclusion: These findings indicate that celastrol is an effective inhibitor for CRC, regulating the NF-κB/COX-2 pathway, leading to the inhibition of cell proliferation characterized by cell cycle arrest and caspase-dependent apoptosis, providing a potential alternative therapeutic agent for CRC patients.

Serum Starvation Sensitizes Anticancer Effect of Anemarrhena asphodeloides via p38/JNK-Induced Cell Cycle Arrest and Apoptosis in Colorectal Cancer Cells

2021 ◽  
pp. 1-16
Author(s):  
Kon-Young Ji ◽  
Ki Mo Kim ◽  
Yun Hee Kim ◽  
Ki-Shuk Shim ◽  
Joo Young Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Serum Starvation ◽  
Anticancer Effect ◽  
Cycle Arrest ◽  
Colorectal Cancer Cells ◽  
Anemarrhena Asphodeloides ◽  
Hct116 Cells

The molecular mechanism underlying the anticancer effects of Anemarrhena asphodeloides (A. asphodeloides) on colon cancer is unknown. This is the first study evaluating the anticancer effect of A. asphodeloides extract (AA-Ex) in serum-starved colorectal cancer cells. Changes in cell proliferation and morphology in serum-starved MC38 and HCT116 colorectal cancer cells were investigated using MTS assay. Cell cycle and apoptosis were investigated using flow cytometry, and cell cycle regulator expression was determined using qRT-PCR. Apoptosis regulator protein levels and mitogen-activated protein kinase (MAPK) phosphorylation were assessed using western blotting. AA-Ex sensitively suppressed proliferation of serum-starved colorectal cancer cells, with MC38 and HCT116 cells showing greater changes in proliferation after treatment with AA-Ex under serum starvation than HaCaT and RAW 264.7 cells. AA-Ex inhibited cell cycle progression in serum-starved MC38 and HCT116 cells and increased the expression of cell cycle inhibitors (p53, p21, and p27). Furthermore, AA-Ex induced apoptosis in serum-starved MC38 and HCT116 cells. Consistently, AA-Ex suppressed the expression of the anti-apoptotic molecule Bcl-2 and upregulated pro-apoptotic molecules (cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved-PARP) in serum-starved cells. AA-Ex treatment under serum starvation decreased AKT and ERK1/2 phosphorylation in the cell survival signaling pathway but increased p38 and JNK phosphorylation. Furthermore, AA-Ex treatment with serum starvation increased the levels of the transcription factors of the p38 and JNK pathway. Serum starvation sensitizes colorectal cancer cells to the anticancer effect of A. asphodeloidesvia p38/JNK-induced cell cycle arrest and apoptosis. Hence, AA-Ex possesses therapeutic potential for colon cancer treatment.

Down-Regulation of Asparagine Synthetase Induces Cell Cycle Arrest and Inhibits Cell Proliferation of Breast Cancer

2014 ◽  
Vol 84 (5) ◽  
pp. 578-584 ◽  
Author(s):  
Hongjian Yang ◽  
Xiangming He ◽  
Yabing Zheng ◽  
Weiliang Feng ◽  
Xianghou Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Asparagine Synthetase ◽  
Down Regulation ◽  
Cycle Arrest

scholarly journals Circular RNA hsa_circ_102209 promotes the growth and metastasis of colorectal cancer through miR-761-mediated Ras and Rab interactor 1 signaling

2020 ◽  
Author(s):  
CHI LI ◽  
Hong Zhou
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Quantitative Polymerase Chain Reaction ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Colonic Epithelial Cells ◽  
Cycle Arrest

Abstract Background: In our study, has_circ_102209 was the most upregulated gene in colorectal cancer (CRC) tissues according to circRNA array data. The levels of hsa_circ_102209 in CRC specimens and cells, as well as its effects on CRC cells were investigated. Methods: The expression of hsa_circ_102209 in CRC and paired non-cancerous samples, human CRC and normal colonic epithelial cells were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cells with hsa_circ_102209 knockdown were established using lentiviral vectors . Cell proliferative ability was evaluated using CCK-8 assay; cell migration and invasion were assessed by wound healing and Transwell assay. Cell cycle arrest and apoptosis were determined; apoptosis and EMT markers were examined using RT-qPCR and western blotting. Tumour development and levels of associated proteins were determined in hsa_circ_102209 knockdown mice. Results: Our results revealed that expression of hsa_circ_102209 was remarkably increased in CRC tissues, where the levels of miR-761 were notably reduced (p<0.05). Additionally, the levels of hsa_circ_102209 was associated with tumor stage and occurrence of liver metastasis in CRC patients, and the expression of hsa_circ_102209 and miR-761 were negatively correlated (p<0.05). Moreover, hsa_circ_102209 was upregulated in CRC cell s compared with normal colonic epithelial cells. Knockdown of hsa_circ_102209 notably inhibited the proliferation, migration, invasion and EMT of CRC cell s (p<0.05), whereas enhanced cell cycle arrest at G0/G1 phase and apoptosis (p<0.05). Furthermore, miR-761/ Ras and Rab interactor 1 ( RIN1) axis was the putative target of hsa_circ_102209 in CRC and involved in hsa_circ_102209 -modulated growth and metastasis in CRC cell s (p<0.05). Knockdown of hsa_circ_102209 also remarkably suppressed tumor growth in vivo (p<0.05). Conclusions: our data revealed that the expression of hsa_circ_102209 was elevated in CRC samples and cells. Furthermore, hsa_circ_102209 could promote the progression of CRC through miR-761/RIN1 axis. More importantly, hsa_circ_102209 /miR-761/RIN1 signaling may be a novel therapeutic target for the treatment of CRC patients .

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.

scholarly journals Circular RNA hsa_circ_102209 promotes the growth and metastasis of colorectal cancer through miR-761-mediated Ras and Rab interactor 1 signaling

2020 ◽  
Author(s):  
CHI LI ◽  
Hong Zhou
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Quantitative Polymerase Chain Reaction ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Colonic Epithelial Cells ◽  
Cycle Arrest

Abstract Background: The levels of hsa_circ_102209 in colorectal cancer (CRC) specimens and cells, as well as its effects on CRC cells were investigated. Methods: The expression of hsa_circ_102209 in CRC and paired non-cancerous samples, human CRC and normal colonic epithelial cells were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cells with hsa_circ_102209 knockdown were established using lentiviral vectors. Cell proliferative ability was evaluated using CCK-8 assay; cell migration and invasion were assessed by wound healing and Transwell assay. Cell cycle arrest and apoptosis were determined; apoptosis and EMT markers were examined using RT-qPCR and western blotting. Tumour development and levels of associated proteins were determined in hsa_circ_102209 knockdown mice. Results: Our results revealed that expression of hsa_circ_102209 was remarkably increased in CRC tissues, where the levels of miR-761 were notably reduced (p<0.05). Additionally, the levels of hsa_circ_102209 was associated with histology grade and occurrence of liver metastasis in CRC patients, and the expression of hsa_circ_102209 and miR-761 were negatively correlated (p<0.05). Moreover, hsa_circ_102209 was upregulated in CRC cells compared with normal colonic epithelial cells. Knockdown of hsa_circ_102209 notably inhibited the proliferation, migration, invasion and EMT of CRC cells (p<0.05), whereas enhanced cell cycle arrest at G0/G1 phase and apoptosis (p<0.05). Furthermore, miR-761/Ras and Rab interactor 1 (RIN1) axis was the putative target of hsa_circ_102209 in CRC and involved in hsa_circ_102209-modulated growth and metastasis in CRC cells (p<0.05). Knockdown of hsa_circ_102209 also remarkably suppressed tumor growth in vivo (p<0.05). Conclusions: our data revealed that the expression of hsa_circ_102209 was elevated in CRC samples and cells. Furthermore, hsa_circ_102209 could promote the progression of CRC through miR-761/RIN1 axis. More importantly, hsa_circ_102209/miR-761/RIN1 signaling may be a novel therapeutic target for the treatment of CRC patients.

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