| Title: |
Gliotoxin Is a Dual Inhibitor of Farnesyltransferase and Geranylgeranyltransferase I with Antitumor Activity Against Breast Cancer In Vivo |
| Authors: |
Vigushin, DM; Mirsaidi, N; Brooke, G; Sun, C; Pace, P; Inman, L; Moody, CJ; Coombes, RC |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2004 |
| Collection: |
University of Essex Research Repository |
| Subject Terms: |
RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Description: |
Gliotoxin is a natural mycotoxin with immunosuppressive and antimicrobial activity. Inhibition of farnesyltransferase (IC 50 80 μM) and geranylgeranyltransferase I (IC 50 17 μM) stimulated interest in the potential antitumor activity of this epidithiodioxopiperazine. Gliotoxin inhibited proliferation of six breast cancer cell lines in culture with mean ± SD IC 50 289 ± 328 μM (range 38-985 μM); intracellular farnesylation of Lamin B and geranylgeranylation of Rap1A were inhibited in a dose-dependent manner. In randomized controlled studies using the N-methyl-N-nitrosourea rat mammary carcinoma model, gliotoxin had pronounced antitumor activity in vitro and little systemic toxicity when administered to 10 animals at 10 mg/kg by subcutaneous injection weekly for 4 wk compared with 10 controls. Single doses up to 25 mg/kg were well tolerated. The present studies confirm that gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with pronounced antitumor activity and favorable toxicity profile against breast cancer in vitro and in vivo. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
Vigushin, DM and Mirsaidi, N and Brooke, G and Sun, C and Pace, P and Inman, L and Moody, CJ and Coombes, RC (2004) Gliotoxin Is a Dual Inhibitor of Farnesyltransferase and Geranylgeranyltransferase I with Antitumor Activity Against Breast Cancer In Vivo. Medical Oncology, 21 (1). pp. 21-30. DOI https://doi.org/10.1385/mo:21:1:21 |
| DOI: |
10.1385/mo:21:1:21 |
| Availability: |
https://repository.essex.ac.uk/8309/; https://doi.org/10.1385/mo:21:1:21 |
| Accession Number: |
edsbas.A75F8480 |
| Database: |
BASE |