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| Item Type: | Article |
|---|---|
| Title: | In-vitro and in-vivo investigations into the carbene-gold anticancer drug candidates NHC*-Au-SCSNMe(2) and NHC*-Au-S-GLUC against advanced prostate cancer PC3 |
| Creators Name: | Walther, W., Althagafi, D., Curran, D., O'Beirne, C., Mc Carthy, C., Ott, I., Basu, U., Büttner, B., Sterner-Kock, A., Müller-Bunz, H., Sánchez-Sanz, G., Zhu, X. and Tacke, M. |
| Abstract: | The anticancer drug candidates 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene gold(I) dimethylamino dithiocarbamate and 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-1-thiolate derivative exhibited nanomolar in-vitro activity against prostate cancer cells advanced prostate cancer (PC3) and micromolar inhibition of mammalian thioredoxin reductase. Encouraging maximum tolerable dose experiments led to human prostate cancer subcutaneous xenograft experiments; 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene gold(I) dimethylamino dithiocarbamate and 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-1-thiolate derivative were applied twelve times at two doses in groups of n = 5 PC3 to tumor-bearing NMRI:nu/nu mice. 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene gold(I) dimethylamino dithiocarbamate and 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-1-thiolate derivative at the dose of 10 and 20 mg/kg showed good tolerability, while no significant body weight loss was seen in both groups. In particular, for the drug 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene gold(I) dimethylamino dithiocarbamate the tumor growth inhibition suggested to be dose dependent, reflected by the respective optimal T/C values of 0.45 at the dose of 10 mg/kg and of 0.31 at the dose of 20 mg/kg. By contrast, the 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-1-thiolate derivative treated groups showed no indication for dose-dependent antitumoral activity, as reflected by the optimal T/C values of 0.44 for the 10 mg/kg and for the 20 mg/kg treated mice. Immunohistochemical experiments involving Ki67 staining of tumor tissue showed that both compounds reduced PC3 cell proliferation against the difficult to treat advanced human prostate tumors derived from PC3. |
| Keywords: | Carbene-Gold Anticancer Drug, NCI 60 Cancer Cell Panel, Advanced Prostate Cancer, Thioredoxin Reductase, Xenograft Mouse Model, Animals, Mice |
| Source: | Anti-Cancer Drugs |
| ISSN: | 0959-4973 |
| Publisher: | Lippincott Williams & Wilkins |
| Volume: | 31 |
| Number: | 7 |
| Page Range: | 672-683 |
| Date: | August 2020 |
| Official Publication: | https://doi.org/10.1097/CAD.0000000000000930 |
| PubMed: | View item in PubMed |
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