scholarly journals Investigation of the Effect of IRAK1/4 Inhibitor on the Expression of P53, Bcl-2, Bax and GALNT14 Genes in Combination with Methotrexate and Topotecan in Breast Cancer Cell Lines

2020 ◽  
Vol 11 (2) ◽  
pp. 9157-9169
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Interleukin 1 ◽  
P53 Gene ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

Breast cancer is the most common cancer among women. Chemotherapy is one of the main methods of breast cancer treatment, but its efficacy is affected by drug resistance. Interleukin-1 receptor-dependent kinases (IRAKs) are associated with drug resistance in cancer cells. The aim of this study was to investigate the relationship between the expression of p53, Bax, Bcl-2, and GALANT14 in treatment with Methotrexate and Topotecan alone and in combination with IRAK1/4 inhibitor. BT20, BT549, and MB468 breast cancer cell lines were cultured in a specific culture medium, and the effects of Methotrexate and Topotecan with or without IRAK1/4 inhibition on the expression of P53, Bcl-2, Bax, and GALNT14 genes was evaluated by Real-Time PCR. RT-qPCR results showed that the administration of IRAK1/4 inhibitor increased the expression of p53 in all three cell lines treated with Methotrexate and Topotecan. IRAK1/4 inhibitor increased the efficacy of Methotrexate and Topotecan on p53 gene expression. The expression level of the Bcl2 gene was significantly increased in the MB468 cell line treated with Topotecan and IRAK inhibitor + Methotrexate. In the present study, it was found that the IRAK1/4 inhibitor increased the efficacy of Methotrexate and Topotecan on p53 gene expression, thereby inducing apoptosis.

scholarly journals Molecular Simulations Identify Target Receptor Kinases Bound by Astaxanthin to Induce Breast Cancer Cell Apoptosis

2020 ◽  
pp. 72-82
Author(s):  
Mossa Gardaneh ◽  
Zahra Nayeri ◽  
Parvin Akbari ◽  
Mahsa Gardaneh ◽  
Hasan Tahermansouri
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Combination Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Breast Cancer Cell Lines

Background: We investigated molecular mechanisms behind astaxanthinmediated induction of apoptosis in breast cancer cell lines toward combination therapy against cancer drug resistance. Methods: Breast cancer cell lines were treated with serial concentrations of astaxanthin to determine its IC50. We used drug-design software to predict interactions between astaxanthin and receptor tyrosine kinases or other key gene products involved in intracellular signaling pathways. Changes in gene expression were examined using RT-PCR. The effect of astaxanthin-nanocarbons combinations on cancer cells was also evaluated. Results: Astaxanthin induced cell death in all three breast cancer cell lines was examined so that its IC50 in two HER2-amplifying lines SKBR3 and BT-474 stood, respectively, at 36 and 37 ?M; however, this figure for MCF-7 was significantly lowered to 23 ?M (P<0.05). Astaxanthin-treated SKBR3 cells showed apoptotic death upon co-staining. Our in silico examinations showed that some growth-promoting molecules are strongly bound by astaxanthin via their specific amino acid residues with their binding energy standing below -6 KCa/Mol. Next, astaxanthin was combined with either graphene oxide or carboxylated multi-walled carbon nanotube, with the latter affecting SKBR cell survival more extensively than the former (P<0.05). Finally, astaxanthin coinduced tumor suppressors p53 and PTEN but downregulated the expression of growth-inducing genes in treated cells. Conclusion: These findings indicate astaxanthin carries' multitarget antitumorigenic capacities and introduce the compound as a suitable candidate for combination therapy regimens against cancer growth and drug resistance. Development of animal models to elucidate interactions between the compound and tumor microenvironment could be a major step forward towards the inclusion of astaxanthin in cancer therapy trials.

scholarly journals Gene expression profiling of breast cancer cell lines treated with proton and electron radiations

2018 ◽  
pp. 20170934 ◽  
Author(s):  
Valentina Bravatà ◽  
Luigi Minafra ◽  
Francesco Paolo Cammarata ◽  
Pietro Pisciotta ◽  
Debora Lamia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Profiling ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Expression Profiling ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

scholarly journals Identification of novel microtubule inhibitors effective in fission yeast and human cells and their effects on breast cancer cell lines

Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 210161
Author(s):  
Jun Morishita ◽  
Paul Nurse
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Fission Yeast ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Intracellular Transport ◽  
Cancer Cell Lines ◽  
Human Cells ◽  
Breast Cancer Cell Lines

Microtubules are critical for a variety of cellular processes such as chromosome segregation, intracellular transport and cell shape. Drugs against microtubules have been widely used in cancer chemotherapies, though the acquisition of drug resistance has been a significant issue for their use. To identify novel small molecules that inhibit microtubule organization, we conducted sequential phenotypic screening of fission yeast and human cells. From a library of diverse 10 371 chemicals, we identified 11 compounds that inhibit proper mitotic progression both in fission yeast and in HeLa cells. An in vitro assay revealed that five of these compounds are strong inhibitors of tubulin polymerization. These compounds directly bind tubulin and destabilize the structures of tubulin dimers. We showed that one of the compounds, L1, binds to the colchicine-binding site of microtubules and exhibits a preferential potency against a panel of human breast cancer cell lines compared with a control non-cancer cell line. In addition, L1 overcomes cellular drug resistance mediated by βIII tubulin overexpression and has a strong synergistic effect when combined with the Plk1 inhibitor BI2536. Thus, we have established an economically effective drug screening strategy to target mitosis and microtubules, and have identified a candidate compound for cancer chemotherapy.

scholarly journals Human Arylamine N-Acetyltransferase 1 (NAT1) Knockout in MDA-MB-231 Breast Cancer Cell Lines Leads to Transcription of NAT2

2022 ◽  
Vol 12 ◽  
Author(s):  
Samantha M. Carlisle ◽  
Patrick J. Trainor ◽  
Mark A. Doll ◽  
David W. Hein
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Differential Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Global Gene Expression ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Metabolizing Enzyme

Many cancers, including breast cancer, have shown differential expression of human arylamine N-acetyltransferase 1 (NAT1). The exact effect this differential expression has on disease risk and progression remains unclear. While NAT1 is classically defined as a xenobiotic metabolizing enzyme, other functions and roles in endogenous metabolism have recently been described providing additional impetus for investigating the effects of varying levels of NAT1 on global gene expression. Our objective is to further evaluate the role of NAT1 in breast cancer by determining the effect of NAT1 overexpression, knockdown, and knockout on global gene expression in MDA-MB-231 cell lines. RNA-seq was utilized to interrogate differential gene expression (genes correlated with NAT1 activity) across three biological replicates of previously constructed and characterized MDA-MB-231 breast cancer cell lines expressing parental (Scrambled), increased (Up), decreased (Down, CRISPR 2–12), or knockout (CRISPR 2–19, CRISPR 5–50) levels of NAT1. 3,889 genes were significantly associated with the NAT1 N-acetylation activity of the cell lines (adjusted p ≤ 0.05); of those 3,889 genes, 1,756 were positively associated with NAT1 N-acetylation activity and 2,133 were negatively associated with NAT1 N-acetylation activity. An enrichment of genes involved in cell adhesion was observed. Additionally, human arylamine N-acetyltransferase 2 (NAT2) transcripts were observed in the complete NAT1 knockout cell lines (CRISPR 2–19 and CRISPR 5–50). This study provides further evidence that NAT1 functions as more than just a drug metabolizing enzyme given the observation that differences in NAT1 activity have significant impacts on global gene expression. Additionally, our data suggests the knockout of NAT1 results in transcription of its isozyme NAT2.

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