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Pharmaceuticals 2011, 4(11), 1488-1502; doi:10.3390/ph4111488

Photodynamic Therapy with Hypericin Improved by Targeting HSP90 Associated Proteins

1 Laboratory of Cell Biology, Institute of Biology and Ecology, Faculty of Sciences, P.J. Šafárik University, 040 01 Košice, Slovak Republic 2 Geriatric Nursing Clinic, Faculty of Medicine, P.J. Šafárik University, 040 01 Košice, Slovak Republic 3 Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University,040 01 Košice, Slovak Republic
* Author to whom correspondence should be addressed.
Received: 1 September 2011 / Revised: 1 November 2011 / Accepted: 7 November 2011 / Published: 10 November 2011
(This article belongs to the Special Issue Hsp90 Inhibitors)
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In this study we have focused on the response of SKBR-3 cells to both single 17-DMAG treatment as well as its combination with photodynamic therapy with hypericin. Low concentrations of 17-DMAG without any effect on survival of SKBR-3 cells significantly reduced metabolic activity, viability and cell number when combined with photodynamic therapy with hypericin. Moreover, IC10 concentation of 17-DMAG resulted in significant increase of SKBR-3 cells in G1 phase of the cell cycle, followed by an increase of cells in G2 phase when combined with photodynamic therapy. Furthermore, 17-DMAG already decreased HER2, Akt, P-Erk1/2 and survivin protein levels in SKBR-3 cells a short time after its application. In this regard, 17-DMAG protected also SKBR-3 cells against both P-Erk1/2 as well as survivin upregulations induced by photodynamic therapy with hypericin. Interestingly, IC10 concentration of 17-DMAG led to total depletion of Akt, P-Erk1/2 proteins and to decrease of survivin level at 48 h. On the other hand, 17-DMAG did not change HER2 relative expression in SKBR-3 cells, but caused a significant decrease of HER2 mRNA in MCF-7 cells characterized by low HER2 expression. These results show that targeting HSP90 client proteins increases the efficiency of antineoplastic effect of photodynamic therapy in vitro.
Keywords: hypericin-PDT; 17-DMAG; HSP90 hypericin-PDT; 17-DMAG; HSP90
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Solár, P.; Chytilová, M.; Solárová, Z.; Mojžiš, J.; Ferenc, P.; Fedoročko, P. Photodynamic Therapy with Hypericin Improved by Targeting HSP90 Associated Proteins. Pharmaceuticals 2011, 4, 1488-1502.

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