Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins

Authors

• Yu-Dong Zhou, Shanghai University of Traditional Chinese Medicine; University of Mississippi
• Jun Li, University of Mississippi
• Lin Du, University of Mississippi
• Fakhri Mahdi, University of Mississippi
• Thuy P. Le, University of Mississippi
• Wei-Lun Chen, University of Illinois at Chicago
• Steven M. Swanson, University of Wisconsin-Madison
• Kounosuke Watabe, Wake Forest University
• Dale G. Nagle, Shanghai University of Traditional Chinese Medicine; University of Mississippi

Department

Pharmacy

Document Type

Article

DOI

10.3390/md16110442

Publication Date

11-10-2018

Abstract

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery.

Relational Format

journal article

Recommended Citation

Zhou, Y.-D., Li, J., Du, L., Mahdi, F., Le, T. P., Chen, W.-L., Swanson, S. M., Watabe, K., & Nagle, D. G. (2018). Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins. Marine Drugs, 16(11), 442. https://doi.org/10.3390/md16110442

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