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 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 The Synergistic Effects of SHR6390 Combined With Pyrotinib on HER2+/HR+ Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yukun Wang ◽  
Xiang Yuan ◽  
Jing Li ◽  
Zhiwei Liu ◽  
Xinyang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Cancer Cell Lines ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

HER2+/HR+ breast cancer is a special molecular type of breast cancer. Existing treatment methods are prone to resistance; “precision treatment” is necessary. Pyrotinib is a pan-her kinase inhibitor that can be used in HER2-positive tumors, while SHR6390 is a CDK4/6 inhibitor that can inhibit ER+ breast cancer cell cycle progression and cancer cell proliferation. In cancer cells, HER2 and CDK4/6 signaling pathways could be nonredundant; co-inhibition of both pathways by combination of SHR6390 and pyrotinib may have synergistic anticancer activity on HER2+/HR+ breast cancer. In this study, we determined the synergy of the two-drug combination and underlying molecular mechanisms. We showed that the combination of SHR6390 and pyrotinib synergistically inhibited the proliferation, migration, and invasion of HER2+/HR+ breast cancer cells in vitro. The combination of two drugs induced G1/S phase arrest and apoptosis in HER2+/HR+ breast cancer cell lines. The combination of two drugs prolonged the time to tumor recurrence in the xenograft model system. By second-generation RNA sequencing technology and enrichment analysis of the pyrotinib-resistant cell line, we found that FOXM1 was associated with induced resistance to HER2-targeted therapy. In HER2+/HR+ breast cancer cell lines, the combination of the two drugs could further reduce FOXM1 phosphorylation, thereby enhancing the antitumor effect to a certain extent. These findings suggest that SHR6390 combination with pyrotinib suppresses the proliferation, migration, and invasion of HER2+/HR+ breast cancers through regulation of FOXM1.

scholarly journals A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

2021 ◽  
Vol 22 (10) ◽  
pp. 5255
Author(s):  
Adele Chimento ◽  
Anna Santarsiero ◽  
Domenico Iacopetta ◽  
Jessica Ceramella ◽  
Arianna De Luca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Antiproliferative Effects

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.

scholarly journals Soy Isoflavones and Breast Cancer Cell Lines: Molecular Mechanisms and Future Perspectives

Molecules ◽  
2015 ◽  
Vol 21 (1) ◽  
pp. 13 ◽  
Author(s):  
Alina Uifălean ◽  
Stefanie Schneider ◽  
Corina Ionescu ◽  
Michael Lalk ◽  
Cristina Iuga
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Cell Lines ◽  
Soy Isoflavones ◽  
Breast Cancer Cell Lines ◽  
Future Perspectives

Acyl-CoA synthetase-4 is implicated in drug resistance in breast cancer cell lines involving the regulation of energy-dependent transporter expression

2019 ◽  
Vol 159 ◽  
pp. 52-63 ◽  
Author(s):  
Ulises Daniel Orlando ◽  
Ana Fernanda Castillo ◽  
Mayra Agustina Ríos Medrano ◽  
Angela Rosaria Solano ◽  
Paula Mariana Maloberti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Energy Dependent ◽  
Transporter Expression

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 Combination treatment with a PI3K/Akt/mTOR pathway inhibitor overcomes resistance to anti-HER2 therapy in PIK3CA-mutant HER2-positive breast cancer cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yumi Fujimoto ◽  
Tomoko Yamamori Morita ◽  
Akihiro Ohashi ◽  
Hiroshi Haeno ◽  
Yumi Hakozaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Single Agent ◽  
Cancer Cell Lines ◽  
Pi3k Pathway ◽  
Breast Cancer Cell Lines ◽  
Her2 Breast Cancer

AbstractAmplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) are observed in 15–20% of breast cancers (HER2+ breast cancers), and anti-HER2 therapies have significantly improved prognosis of patients with HER2+ breast cancer. One resistance mechanism to anti-HER2 therapies is constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway. Combination therapy with small-molecule inhibitors of AKT and HER2 was conducted in HER2+ breast cancer cell lines with or without PIK3CA mutations, which lead to constitutive activation of the PI3K pathway. PIK3CA mutations played important roles in resistance to single-agent anti-HER2 therapy in breast cancer cell lines. Combination therapy of a HER2 inhibitor and an AKT inhibitor, as well as other PI3K pathway inhibitors, could overcome the therapeutic limitations associated with single-agent anti-HER2 treatment in PIK3CA-mutant HER2+ breast cancer cell lines. Furthermore, expression of phosphorylated 4E-binding protein 1 (p4EBP1) following the treatment correlated with the antiproliferative activities of the combination, suggesting that p4EBP1 may have potential as a prognostic and/or efficacy-linking biomarkers for these combination therapies in patients with HER2+ breast cancer. These findings highlight potential clinical strategies using combination therapy to overcome the limitations associated with single-agent anti-HER2 therapies in patients with HER2+ breast cancer.

GDC-0941 and CXCL8 (3-72) K11R/G31P combination therapy confers enhanced efficacy against breast cancer

2020 ◽  
Vol 16 (14) ◽  
pp. 911-921
Author(s):  
Xiaodong Li ◽  
Yuanyue Zhang ◽  
Williams Walana ◽  
Feng Zhao ◽  
Fang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Combined Treatment ◽  
Cancer Cell Lines ◽  
Pi3k Inhibitor ◽  
Phase Cell ◽  
Breast Cancer Cell Lines

Aim: Herein is presented the combined effect of PI3K inhibitor (GDC-0941) and CXCR1/2 analogue (G31P) in breast cancer. Materials & methods: Breast cancer cell lines and xenograft model were employed to test the efficacy of the combination therapy. Results: GDC-0941+G31P treatment substantially inhibited multiplication of all the breast cancer cell lines used in this study (BT474, HCC1954 and 4T1). Even though single therapies caused a meaningful S-phase cell cycle arrest, the inhibition effect was more potent with the combined treatment. Similarly, enhanced apoptosis accompanied GDC-0941+G31P treatment. Furthermore, the migration ability of the breast cancer cell lines were significantly curtailed by the combination therapy compared with the single treatments. Conclusion: The findings suggest that combination treatment involving PI3K inhibitor and CXCR1/2 analogue (G31P) could be a potent therapeutic option for breast cancer treatment.

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