+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Debio-0932, a second generation oral Hsp90 inhibitor, induces apoptosis in MCF-7 and MDA-MB-231 cell lines.

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Heat shock protein 90 (Hsp90) is a key chaperone that is abnormally expressed in cancer cells, and therefore, designing novel compounds to inhibit chaperone activities of the Hsp90 is a promising therapeutic approach for cancer drug discovery. Debio-0932 is a second-generation Hsp90 inhibitor that exhibited promising anticancer activity against a wide variety of cancer types with a strong binding affinity for Hsp90 and high oral bioavailability. Anticancer activities of the Debio-0932 were tested in MCF-7 and MDA-MB-231 cell lines. Molecular docking results indicated that Debio-0932 was selectively bound to the ATP binding pocket of the Hsp90 with an estimated free energy of binding - 7.24 kcal/mol. Antiproliferative activity of Debio-0932 was determined by XTT assay and Debio-0932 exhibited a cytotoxic effect on MCF-7 and MDA-MB-231 cells in a time and dose-depended manner. Apoptosis inducer role of Debio-0932 was evaluated in MCF-7 and MDA-MB-231 cells with fluorometric apoptosis/necrosis detection kit. Treatment with Debio-0932 stimulated apoptosis in both breast cancer cell lines. mRNA and protein expression levels of Bax, Bcl-2 and Casp-9 were determined in MCF-7 and MDA-MB-231 cells by RT-PCR and Western blotting respectively. Debio-0932 stimulated the down-regulation of anti-apoptotic protein Bcl-2 and the up-regulation of apoptotic protein Bax and cleavage of Casp-9 in cancer cells. Moreover, the anti-invasive potential of Debio-0932 was evaluated in endothelial cells (HUVEC) by wound-healing assay. Debio-0932 decreased the migration of HUVEC cells as compared to the control group. These results indicate that Debio-0932 is a promising compound to treat triple-negative breast cancer and hormone receptor-positive breast cancer, and their metastases.

          Related collections

          Author and article information

          Mol Biol Rep
          Molecular biology reports
          Springer Science and Business Media LLC
          Apr 2021
          : 48
          : 4
          [1 ] Department of Veterinary Medicine, Laboratory and Veterinary Health Program, Artova Vocational School, Tokat Gaziosmanpaşa University, Tokat, Turkey. aykut.ozgur@gop.edu.tr.
          [2 ] TUBITAK Marmara Research Center, Gene Engineering and Biotechnology Institute, Gebze, Turkey.
          [3 ] Department of Biomaterials and Tissue Engineering, Faculty of Engineering and Architecture, Tokat Gaziosmanpaşa University, Tokat, Turkey.
          [4 ] Division of Medical Biology, Department of Basic Medical Sciences, Hamidiye Faculty of Medicine, University of Health Sciences, Turkey, Istanbul, Turkey.
          [5 ] Experimental Medicine Application & Research Center, Validebag Research Park, University of Health Sciences, Istanbul, Turkey.
          [6 ] Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Tokat Gaziosmanpaşa University, Tokat, Turkey.

          MDA-MB-231,Breast cancer,Chemotherapy,Debio-0932,Hsp90,MCF-7
          MDA-MB-231, Breast cancer, Chemotherapy, Debio-0932, Hsp90, MCF-7


          Comment on this article