scholarly journals Treatment of Breast and Colon Cancer Cell Lines with Anti-Helmintic Benzimidazoles Mebendazole or Albendazole Results in Selective Apoptotic Cell Death

2021 ◽  
Author(s):  
Jakeb SSM Petersen ◽  
Sarah Baird
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Cycle Arrest ◽  
Colon Cancer Cell Lines ◽  
Ht 29

Abstract Purpose: Anti-helmintic drugs mebendazole and albendazole are commonly used to treat a variety of parasitic infestations. They have recently shown some promising results in pre-clinical in vitro and in vivo anti-cancer studies. We compare their efficacy in breast and colon cancer cell lines as well as in non-cancerous cells and elucidate their mechanism of action. Methods: The drugs were screened for cytotoxicity in MDA-MB-231, MCF-7 (breast cancer), HT-29 (colorectal cancer) and mesenchymal stem cells, using the MTT assay. Their effects on the cell cycle, tubulin levels and cell death mechanisms were analysed using flow cytometry and fluorescent microscopy. Results: Mebendazole and albendazole were found to selectively kill cancer cells, being most potent in the colorectal cancer cell line HT-29, with both drugs having IC50 values of less than 1 µM at 48 hours. Both mebendazole and albendazole induced classical apoptosis characterised by caspase-3 activation, phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane permeability and reactive oxygen species production. Cell cycle arrest in the G2/M phase was found, and tubulin polymerisation was disrupted.Conclusion: Mebendazole and albendazole cause selective cancer cell death via a mechanism of classical apoptosis and cell cycle arrest, which involves the destabilisation of microtubules.

scholarly journals MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

2020 ◽  
Author(s):  
Fuda Huang ◽  
Mingwei Wei ◽  
Anmin Wang ◽  
Ya Zhang ◽  
Zebang Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Expression Levels ◽  
Colon Cancer Cell Lines ◽  
Cancer Tissues

Abstract BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.

scholarly journals Superior Inhibitory Efficacy of Butyrate over Propionate and Acetate Against Human Colon Cancer Cell Proliferation via Cell Cycle Arrest and Apoptosis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 364-364
Author(s):  
Huawei Zeng ◽  
Stephanie Hamlin ◽  
Bryan Safratowich ◽  
Wen-Hsing Cheng ◽  
LuAnn Johnson
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Hct116 Cell ◽  
Colon Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Human Colon Cancer ◽  
Cycle Arrest

Abstract Objectives Intake of fiber has beneficial properties for gut health. These effects may be due to the increased production of short chain fatty acids (SCFAs) such as acetate, propionate and butyrate during dietary fiber fermentation in the colon. We tested the hypothesis that butyrate exhibits a stronger inhibitory potential against colon cancer cell proliferation compared with acetate and propionate. Methods With a human HCT116 colon cancer cell culture model, we used cell cycle, apoptosis, PCR array, biochemical, western blotting and immunofluorescent assays to determine SCFAs’ inhibitory effects on HCT116 cell proliferation. Results We determined the half maximal inhibitory concentrations (IC50) of SCFAs in HCT116 cell proliferation by examining cell growth curves. At 24- and 48- hour time points, IC50 (mM) concentrations of acetate, propionate and butyrate were [66.0 and 29.0], [9.2 and 3.6] and [2.5 and 1.3], respectively.  Consistent with the greater anti-proliferative effect, butyrate exhibits &gt;3-fold stronger potential for inducing cell cycle arrest (including c-Myc/p21 signaling) and apoptosis when compared with acetate and propionate. Subsequently, we focused on the effect of butyrate on apoptotic gene expression. Using a PCR array analysis, we identified 17 pro-apoptotic genes, 6 anti-apoptotic genes, and 4 cellular mediator genes with &gt;1-fold increase or decrease in mRNA levels out of 93 apoptosis related genes in butyrate-treated HCT116 cells when compared with untreated HCT116 cells. These genes were mainly involved in the tumor necrosis factor alpha receptor, NFκB, caspase recruitment domain-containing protein and B-cell lymphoma-2 regulated pathways. Conclusions Collectively, we demonstrated a greater inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis. Funding Sources This work was supported by U.S. Department of Agriculture, Agricultural Research Service, research project 3062–51,000-056–00D.

Lentivirus-mediated siRNA targeting SAE1 induces cell cycle arrest and apoptosis in colon cancer cell RKO

2014 ◽  
Vol 48 (1) ◽  
pp. 91-98 ◽  
Author(s):  
N. Song ◽  
X. -D. Gu ◽  
Y. Wang ◽  
Z. -Y. Chen ◽  
L. -B. Shi
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Cycle Arrest

scholarly journals Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 771 ◽  
Author(s):  
Verónica Ruiz-Torres ◽  
Celia Rodríguez-Pérez ◽  
María Herranz-López ◽  
Beatriz Martín-García ◽  
Ana-María Gómez-Caravaca ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Colon Cancer Cell ◽  
Mitochondrial Depolarization ◽  
Antiproliferative Effects ◽  
Cycle Arrest ◽  
Ros Accumulation

Marine compounds are a potential source of new anticancer drugs. In this study, the antiproliferative effects of 20 invertebrate marine extracts on three colon cancer cell models (HGUE-C-1, HT-29, and SW-480) were evaluated. Extracts from two nudibranchs (Phyllidia varicosa, NA and Dolabella auricularia, NB), a holothurian (Pseudocol ochirus violaceus, PS), and a soft coral (Carotalcyon sp., CR) were selected due to their potent cytotoxic capacities. The four marine extracts exhibited strong antiproliferative effects and induced cell cycle arrest at the G2/M transition, which evolved into early apoptosis in the case of the CR, NA, and NB extracts and necrotic cell death in the case of the PS extract. All the extracts induced, to some extent, intracellular ROS accumulation, mitochondrial depolarization, caspase activation, and DNA damage. The compositions of the four extracts were fully characterized via HPLC-ESI-TOF-MS analysis, which identified up to 98 compounds. We propose that, among the most abundant compounds identified in each extract, diterpenes, steroids, and sesqui- and seterterpenes (CR); cembranolides (PS); diterpenes, polyketides, and indole terpenes (NA); and porphyrin, drimenyl cyclohexanone, and polar steroids (NB) might be candidates for the observed activity. We postulate that reactive oxygen species (ROS) accumulation is responsible for the subsequent DNA damage, mitochondrial depolarization, and cell cycle arrest, ultimately inducing cell death by either apoptosis or necrosis.

scholarly journals SLC7A5 Promotes Colorectal Cancer Progression by Regulating Cell Cycle and Migration

2021 ◽  
Author(s):  
Baiyou Tang ◽  
Lihua Zhang ◽  
Jing Yu ◽  
Mingjing Peng ◽  
Yu Cheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Functional Enrichment ◽  
Public Database ◽  
Colon Cancer Cell Lines

Abstract Background: Solute carrier family 7 member 5 (SLC7A5) was identified highly expressed and as a key participant in various tumor development; however, the role it played in colorectal cancer remains unclear. Methods and Results: In the current study, the expression of SLC7A5 were systematically mined in public databases and validated by real-time PCR in colon cancer and normal tissues. And then, the co-expression and pathway analysis got from public database, which indicated the potential influence of SLC7A5 for the etiology of colorectal cancer, were evaluated in the colon cancer cell lines by loss of SLC7A5 function experiment, flow cytometry, western blot, and wound healing assay. The results showed that the mRNA expression of SLC7A5 was significantly higher in colorectal cancer tissues than that in the non-tumor controls for GEO and TCGA datasets as well as 40 pairs of Xiangya clinical samples. The functional enrichment analysis based on public database showed that the pathways enriched most were cell cycle and epithelial-to-mesenchymal transition (EMT), and Cyclin D1 (CCND1) were the only gene that had a significant positive correlation with SLC7A5. Loss of SLC7A5 function in colon cancer cell lines could arrest cell cycle at G1 phase by down-regulating CCND1 and CDK2 protein expression, and may reduce cell migration by reversing EMT though upregulation of E-Cadherin and downregulation of zonula occludens-1. Conclusion: SLC7A5 is likely associated with the progression of colon cancer.

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