PMID- 30423844 OWN - NLM STAT- MEDLINE DCOM- 20190218 LR - 20190219 IS - 1660-3397 (Electronic) IS - 1660-3397 (Linking) VI - 16 IP - 11 DP - 2018 Nov 10 TI - Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins. LID - 10.3390/md16110442 [doi] LID - 442 AB - 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. Massague 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. FAU - Zhou, Yu-Dong AU - Zhou YD AD - Institute of Interdisciplinary Integrative Medical Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China. ydzhou@olemiss.edu. AD - Department of Chemistry and Biochemistry, University of Mississippi, Oxford, MS 38677-1848, USA. ydzhou@olemiss.edu. FAU - Li, Jun AU - Li J AUID- ORCID: 0000-0001-8243-5267 AD - Department of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677-1848, USA. drlj666@163.com. FAU - Du, Lin AU - Du L AD - Department of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677-1848, USA. Lin.Du-1@ou.edu. FAU - Mahdi, Fakhri AU - Mahdi F AD - Department of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677-1848, USA. fmahdi@olemiss.edu. FAU - Le, Thuy P AU - Le TP AD - Department of Chemistry and Biochemistry, University of Mississippi, Oxford, MS 38677-1848, USA. traceeyle@gmail.com. FAU - Chen, Wei-Lun AU - Chen WL AD - Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. wlchen1003@gmail.com. FAU - Swanson, Steven M AU - Swanson SM AD - Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA. steve.swanson@wisc.edu. FAU - Watabe, Kounosuke AU - Watabe K AD - Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. kwatabe@wakehealth.edu. FAU - Nagle, Dale G AU - Nagle DG AD - Institute of Interdisciplinary Integrative Medical Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China. dnagle@olemiss.edu. AD - Department of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677-1848, USA. dnagle@olemiss.edu. LA - eng GR - CA199016, CA98787, CA125066/National Cancer Institute/ PT - Journal Article DEP - 20181110 PL - Switzerland TA - Mar Drugs JT - Marine drugs JID - 101213729 RN - 0 (Antineoplastic Agents) RN - 0 (Disulfides) RN - 0 (Histone Deacetylase Inhibitors) RN - 110659-91-1 (psammaplin A) RN - 42HK56048U (Tyrosine) RN - EC 3.5.1.98 (Histone Deacetylases) SB - IM MH - Animals MH - Antineoplastic Agents/chemistry/isolation & purification/*pharmacology/therapeutic use MH - Apoptosis/drug effects MH - *Aquatic Organisms MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Culture Techniques/methods MH - Disulfides/chemistry/isolation & purification/*pharmacology/therapeutic use MH - Drug Discovery/methods MH - Drug Screening Assays, Antitumor/methods MH - Female MH - Histone Deacetylase Inhibitors/chemistry/isolation & purification/*pharmacology/therapeutic use MH - Histone Deacetylases/metabolism MH - Humans MH - *Porifera MH - Spheroids, Cellular MH - Triple Negative Breast Neoplasms/*drug therapy MH - Tyrosine/*analogs & derivatives/chemistry/isolation & purification/pharmacology/therapeutic use PMC - PMC6265740 OTO - NOTNLM OT - 3D spheroid invasion OT - HDAC inhibitors OT - HIF OT - VEGFA OT - anti-metastatic OT - bone metastases OT - metastases-specific antitumor agents OT - metastatic organotropism OT - psammaplins OT - triple-negative breast cancer COIS- The authors declare no conflicts of interest. EDAT- 2018/11/15 06:00 MHDA- 2019/02/20 06:00 PMCR- 2018/11/01 CRDT- 2018/11/15 06:00 PHST- 2018/09/13 00:00 [received] PHST- 2018/10/26 00:00 [revised] PHST- 2018/11/09 00:00 [accepted] PHST- 2018/11/15 06:00 [entrez] PHST- 2018/11/15 06:00 [pubmed] PHST- 2019/02/20 06:00 [medline] PHST- 2018/11/01 00:00 [pmc-release] AID - md16110442 [pii] AID - marinedrugs-16-00442 [pii] AID - 10.3390/md16110442 [doi] PST - epublish SO - Mar Drugs. 2018 Nov 10;16(11):442. doi: 10.3390/md16110442.