The expression of NF-kappa B family protein and its relationship with drug resistance in breast cancer cell lines

2003 ◽  
Vol 2 (4) ◽  
pp. 216-218
Author(s):  
Hu Qun ◽  
Kong Xiang
2020 ◽  
pp. 72-82
Author(s):  
Mossa Gardaneh ◽  
Zahra Nayeri ◽  
Parvin Akbari ◽  
Mahsa Gardaneh ◽  
Hasan Tahermansouri

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.


Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 210161
Author(s):  
Jun Morishita ◽  
Paul Nurse

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.


2019 ◽  
Vol 159 ◽  
pp. 52-63 ◽  
Author(s):  
Ulises Daniel Orlando ◽  
Ana Fernanda Castillo ◽  
Mayra Agustina Ríos Medrano ◽  
Angela Rosaria Solano ◽  
Paula Mariana Maloberti ◽  
...  

2020 ◽  
Vol 11 (2) ◽  
pp. 9157-9169

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.


Oncogene ◽  
2002 ◽  
Vol 21 (2) ◽  
pp. 227-238 ◽  
Author(s):  
Silke Radetzki ◽  
Claus-Henning Köhne ◽  
Clarissa von Haefen ◽  
Bernhard Gillissen ◽  
Isrid Sturm ◽  
...  

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity


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