title: Antimetastatic effect of halichondramide, a trisoxazole macrolide from the marine sponge Chondrosia corticata, on human prostate cancer cells via modulation of epithelial-to-mesenchymal transition.
abstract: Halichondramide (HCA), a trisoxazole-containing macrolide isolated from the marine sponge Chondrosia corticata has been shown to exhibit cytotoxicity and antifungal activities. In our previous study, HCA was also found to exhibit antiproliferative activity against a variety of cancer cells. However, the precise mechanism of action of HCA in the antitumor activity remains to be elucidated. In the present study, we identified the antimetastatic activity of HCA in the highly metastatic PC3 human prostate cancer cells. HCA showed potent growth inhibitory activity of the PC3 cells with an IC50 value of 0.81 µM. Further analysis revealed that HCA suppressed the expression of a potential metastatic biomarker, phosphatase of regenerating liver-3 (PRL-3), in PC3 cells. The suppression of PRL-3 by HCA sequentially down-regulates the expression of phosphoinositide 3-kinase (PI3K) subunits p85 and p110. The antimetastatic effect of HCA was also correlated with the down-regulation of matrix metalloproteases (MMPs) and the modulation of cadherin switches N-cadherin and E-cadherin. In addition, HCA also effectively suppressed the migration and invasion of PC3 cells. These findings suggest that halichondramide might serve as a potential inhibitor of tumor cell metastasis with the modulation of PRL-3.
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742, Korea. dicafree5@snu.ac.kr
authors.forename: Yoonho
authors.initials: Y
authors.lastname: Shin
authors.forename: Gi Dae
authors.initials: GD
authors.lastname: Kim
authors.forename: Ju-eun
authors.initials: JE
authors.lastname: Jeon
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011161:Porifera / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015820:Cadherins; D006576:Heterocyclic Compounds, 4 or More Rings; D009363:Neoplasm Proteins; C470372:halichondramide; D019869:Phosphatidylinositol 3-Kinases; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases; D020782:Matrix Metalloproteinases