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Intravasation of SW620 colon cancer cell spheroids through the blood endothelial barrier is inhibited by clinical drugs and flavonoids in vitro

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Abstract
Mechanisms how colorectal cancer (CRC) cells penetrate blood micro-vessel endothelia and metastasise is poorly understood. To study blood endothelial cell (BEC) barrier breaching by CRC emboli, an in vitro assay measuring BEC-free areas underneath SW620 cell spheroids, so called "circular chemorepellent induced defects" (CCIDs, appearing in consequence of endothelial retraction), was adapted and supported by Western blotting, EIA-, EROD- and luciferase reporter assays. Inhibition of ALOX12 or NF-kappa B in SW620 cells or BECs, respectively, caused attenuation of CCIDs. The FDA approved drugs vinpocetine [inhibiting ALOX12-dependent 12(S)-HETE synthesis], ketotifen [inhibiting NF-kappa B], carbamazepine and fenofibrate [inhibiting 12(S)-HETE and NF-kappa B] significantly attenuated CCID formation at low mu M concentrations. In the 5-FU-resistant SW620-R/BEC model guanfacine, nifedipine and proadifen inhibited CCIDs stronger than in the naive SW620/BEC model. This indicated that in SW620-R cells formerly silent (yet unidentified). genes became expressed and targetable by these drugs in course of resistance acquisition. Fenofibrate, and the flavonoids hispidulin and apigenin, which are present in medicinal plants, spices, herbs and fruits, attenuated CCID formation in both, naive- and resistant models. As FDA-approved drugs and food-flavonoids inhibited established and acquired intravasative pathways and attenuated BEC barrier-breaching in vitro, this warrants testing of these compounds in CRC models in vivo.
Keywords
3D model, CRC spheroids, Blood endothelial disintegration, Drug-resistance, FDA approved drugs, Apigenin, JIE-DU-TANG, BREAST-CANCER, MESENCHYMAL TRANSITION, COLORECTAL-CANCER, UP-REGULATION, CYCLE ARREST, RETRACTION, 5-FLUOROURACIL, METASTASIS, APOPTOSIS

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Citation

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Chicago
Holzner, Silvio, Stefan Brenner, Atanas Georgiev Atanasov, Daniel Senfter, Serena Stadler, Chi Huu Nguyen, Adryan Fristiohady, et al. 2018. “Intravasation of SW620 Colon Cancer Cell Spheroids Through the Blood Endothelial Barrier Is Inhibited by Clinical Drugs and Flavonoids in Vitro.” Food and Chemical Toxicology 111: 114–124.
APA
Holzner, S., Brenner, S., Atanasov, A. G., Senfter, D., Stadler, S., Nguyen, C. H., Fristiohady, A., et al. (2018). Intravasation of SW620 colon cancer cell spheroids through the blood endothelial barrier is inhibited by clinical drugs and flavonoids in vitro. FOOD AND CHEMICAL TOXICOLOGY, 111, 114–124.
Vancouver
1.
Holzner S, Brenner S, Atanasov AG, Senfter D, Stadler S, Nguyen CH, et al. Intravasation of SW620 colon cancer cell spheroids through the blood endothelial barrier is inhibited by clinical drugs and flavonoids in vitro. FOOD AND CHEMICAL TOXICOLOGY. 2018;111:114–24.
MLA
Holzner, Silvio, Stefan Brenner, Atanas Georgiev Atanasov, et al. “Intravasation of SW620 Colon Cancer Cell Spheroids Through the Blood Endothelial Barrier Is Inhibited by Clinical Drugs and Flavonoids in Vitro.” FOOD AND CHEMICAL TOXICOLOGY 111 (2018): 114–124. Print.
@article{8572210,
  abstract     = {Mechanisms how colorectal cancer (CRC) cells penetrate blood micro-vessel endothelia and metastasise is poorly understood. To study blood endothelial cell (BEC) barrier breaching by CRC emboli, an in vitro assay measuring BEC-free areas underneath SW620 cell spheroids, so called {\textacutedbl}circular chemorepellent induced defects{\textacutedbl} (CCIDs, appearing in consequence of endothelial retraction), was adapted and supported by Western blotting, EIA-, EROD- and luciferase reporter assays. Inhibition of ALOX12 or NF-kappa B in SW620 cells or BECs, respectively, caused attenuation of CCIDs. The FDA approved drugs vinpocetine [inhibiting ALOX12-dependent 12(S)-HETE synthesis], ketotifen [inhibiting NF-kappa B], carbamazepine and fenofibrate [inhibiting 12(S)-HETE and NF-kappa B] significantly attenuated CCID formation at low mu M concentrations. In the 5-FU-resistant SW620-R/BEC model guanfacine, nifedipine and proadifen inhibited CCIDs stronger than in the naive SW620/BEC model. This indicated that in SW620-R cells formerly silent (yet unidentified). genes became expressed and targetable by these drugs in course of resistance acquisition. Fenofibrate, and the flavonoids hispidulin and apigenin, which are present in medicinal plants, spices, herbs and fruits, attenuated CCID formation in both, naive- and resistant models. As FDA-approved drugs and food-flavonoids inhibited established and acquired intravasative pathways and attenuated BEC barrier-breaching in vitro, this warrants testing of these compounds in CRC models in vivo.},
  author       = {Holzner, Silvio and Brenner, Stefan and Atanasov, Atanas Georgiev and Senfter, Daniel and Stadler, Serena and Nguyen, Chi Huu and Fristiohady, Adryan and Milovanovic, Daniela and Huttary, Nicole and Krieger, Sigurd and Bago-Horvath, Zsuzsanna and De Wever, Olivier and Tentes, Ioannis and {\"O}zmen, Ali and J{\"a}ger, Walter and Dolznig, Helmut and Dirsch, Verena Maria and Mader, Robert Michael and Krenn, Liselotte and Krupitza, Georg},
  issn         = {0278-6915},
  journal      = {FOOD AND CHEMICAL TOXICOLOGY},
  language     = {eng},
  pages        = {114--124},
  title        = {Intravasation of SW620 colon cancer cell spheroids through the blood endothelial barrier is inhibited by clinical drugs and flavonoids in vitro},
  url          = {http://dx.doi.org/10.1016/j.fct.2017.11.015},
  volume       = {111},
  year         = {2018},
}

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