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Mar. Drugs 2013, 11(7), 2472-2485; doi:10.3390/md11072472
Article

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

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Received: 6 May 2013; in revised form: 3 June 2013 / Accepted: 25 June 2013 / Published: 15 July 2013
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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.
Keywords: halichondramide (HCA); antimetastasis; PC3 cells; PRL-3; MMPs halichondramide (HCA); antimetastasis; PC3 cells; PRL-3; MMPs
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Shin, Y.; Kim, G.D.; Jeon, J.-E.; Shin, J.; Lee, S.K. 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. Mar. Drugs 2013, 11, 2472-2485.

AMA Style

Shin Y, Kim GD, Jeon J-E, Shin J, Lee SK. 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. Marine Drugs. 2013; 11(7):2472-2485.

Chicago/Turabian Style

Shin, Yoonho; Kim, Gi D.; Jeon, Ju-eun; Shin, Jongheon; Lee, Sang K. 2013. "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." Mar. Drugs 11, no. 7: 2472-2485.



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