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Mol Cancer Res. 2019 May;17(5):1087-1101. doi: 10.1158/1541-7786.MCR-18-0782. Epub 2019 Jan 7.

Mechanochemical Disruption Suppresses Metastatic Phenotype and Pushes Prostate Cancer Cells toward Apoptosis.

Author information

1
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
2
Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana.
3
Department of Pathology and Laboratory Medicine, Tulane University, New Orleans, Louisiana.
4
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana. damir@tulane.edu.
5
Tulane Cancer Center, Tulane University, New Orleans, Louisiana.
#
Contributed equally

Abstract

Chemical-based medicine that targets specific oncogenes or proteins often leads to cancer recurrence due to tumor heterogeneity and development of chemoresistance. This challenge can be overcome by mechanochemical disruption of cancer cells via focused ultrasound (FUS) and sensitizing chemical agents such as ethanol. We demonstrate that this disruptive therapy decreases the viability, proliferation rate, tumorigenicity, endothelial adhesion, and migratory ability of prostate cancer cells in vitro. It sensitized the cells to TNFR1-- and Fas--mediated apoptosis and reduced the expression of metastatic markers CD44 and CD29. Using a prostate cancer xenograft model, we observed that the mechanochemical disruption led to complete tumor regression in vivo. This switch to a nonaggressive cell phenotype was caused by ROS and Hsp70 overproduction and subsequent impairment of NFκB signaling. FUS induces mechanical perturbations of diverse cancer cell populations, and its combination with agents that amplify and guide remedial cellular responses can stop lethal cancer progression. IMPLICATIONS: Mechanochemical disruption therapy in which FUS is combined with ethanol can be curative for locally aggressive and castration-resistant prostate cancer.

PMID:
30617107
PMCID:
PMC6497535
[Available on 2020-05-01]
DOI:
10.1158/1541-7786.MCR-18-0782

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