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Abstract During the migration of cancer cells for metastasis, cancer cells can be exposed to fluid shear conditions. We examined two breast cancer cell lines, MDA-MB-468 (less metastatic) and MDA-MB-231 (more metastatic), and a benign MCF-10A epithelial cell line for their responsiveness in migration to fluid shear. We tested fluid shear at 15 dyne/cm2 that can be encountered during breast cancer cells traveling through blood vessels or metastasizing to mechanically active tissues such as bone. MCF-10A exhibited the least migration with a trend of migrating in the flow direction. Intriguingly, fluid shear played a potent role as a trigger for MDA-MB-231 cell migration, inducing directional migration along the flow with significantly increased displacement length and migration speed and decreased arrest coefficient relative to unflowed MDA-MB-231. In contrast, MDA-MB-468 cells were markedly less migratory than MDA-MB-231 cells, and responded very poorly to fluid shear. As a result, MDA-MB-468 cells did not exhibit noticeable difference in migration between static and flow conditions, as was distinct in root-mean-square (RMS) displacement—an ensemble average of all participating cells. These may suggest that the difference between more metastatic MDA-MB-231 and less metastatic MDA-MB-468 breast cancer cells could be at least partly involved with their differential responsiveness to fluid shear stimulatory cues. Our study provides new data in regard to potential crosstalk between fluid shear and metastatic potential in mediating breast cancer cell migration.
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Synthesis of Novel Heterocyclic Ferrocenyl Chalcones and Their Biological Evaluation
Breast cancer is currently the most commonlydiagnosed cancer, with 287,850 new cases estimated for 2022 asreported by the American Cancer Society. Therefore, finding aneffective treatment for this disease is imperative. Chalcones are α,β-unsaturated systems found in nature. These compounds haveshown a wide array of biological activities, making them popularsynthetic targets. Chalcones consist of two aromatic substituentsconnected by an enone bridge; this arrangement allows for a largenumber of derivatives. Given the biological relevance of thesecompounds, novel ferrocene-heterocycle-containing chalcones weresynthesized and characterized based on a hybrid drug designapproach. These heterocycles included thiophene, pyrimidine,thiazolyl, and indole groups. Fourteen novel heterocyclic ferrocenyl chalcones were synthesized and characterized. Herein, we alsoreport their cytotoxicity against triple-negative breast cancer cell lines MDA-MB-231 and 4T1 and the noncancer lung cell lineMRC-5. System 3 ferrocenyl chalcones displayed superior anticancer properties compared to their system 1 analogues. System 3chalcones bearing five-membered heterocyclic substituents (thiophene, pyrazole, pyrrole, and pyrimidine) were the most activetoward the MDA-MB-231 cancer cell line with IC50 values from 6.59 to 12.51 μM. Cytotoxicity of the evaluated compounds in the4T1 cell line exhibited IC50 values from 13.23 to 213.7 μM. System 3 pyrazole chalcone had consistent toxicity toward both cell lines(IC50 ∼ 13 μM) as well as promising selectivity relative to the noncancer MRC-5 control. Antioxidant activity was also evaluated,where, contrary to anticancer capabilities, system 1 ferrocenyl chalcones were superior to their system 3 analogues. Antioxidantactivity comparable to that of ascorbic acid was observed for thiophene-bearing ferrocenyl chalcone with EC50 = 31 μM.
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- PAR ID:
- 10535283
- Publisher / Repository:
- American Chemical Societry
- Date Published:
- Journal Name:
- ACS Omega
- Volume:
- 8
- Issue:
- 38
- ISSN:
- 2470-1343
- Page Range / eLocation ID:
- 34377 to 34387
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1021/acsomega.3c01830
