Manumycin and gliotoxin derivative KT7595 block Ras farnesylation and cell growth but do not disturb lamin farnesylation and localization in human tumour cells
| العنوان: | Manumycin and gliotoxin derivative KT7595 block Ras farnesylation and cell growth but do not disturb lamin farnesylation and localization in human tumour cells |
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| المؤلفون: | Yoshiaki Inui, Yukihiko Matsuda, H Mitsui, Yuji Matsuzawa, J Miyagawa, H Ishiguro, Eiji Yamasaki, Toshihiko Nagase, Toshifumi Ito, Sumio Kawata, K. Yamamoto, Shinichi Tamura, M Kinoshita |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Nature Publishing Group, 1997. |
| سنة النشر: | 1997 |
| مصطلحات موضوعية: | Cancer Research, Carcinoma, Hepatocellular, Farnesyl Protein Transferase, Polyunsaturated Alkamides, Immunoblotting, Protein Prenylation, Polyenes, Biology, environment and public health, chemistry.chemical_compound, Gliotoxin, Prenylation, Stomach Neoplasms, Neoplasms, Tumor Cells, Cultured, Humans, Nuclear protein, Enzyme Inhibitors, Fluorescent Antibody Technique, Indirect, Alkyl and Aryl Transferases, DNA synthesis, Cell growth, organic chemicals, Liver Neoplasms, Nuclear Proteins, DNA, Neoplasm, Lamins, Oncology, chemistry, Colonic Neoplasms, Cancer research, ras Proteins, Protein prenylation, lipids (amino acids, peptides, and proteins), Drug Screening Assays, Antitumor, Lamin, Cell Division, Research Article |
| الوصف: | Recently, many inhibitors of farnesyl protein transferase (FPTase) have been identified. Some of them interrupt cell growth in addition to Ras and nuclear lamin processing of Ras-transformed cells. We have tested the effect of the FPTase inhibitors manumycin, an analogue of farnesyl diphosphate, and KT7595, a gliotoxin derivative, on Ras farnesylation, DNA synthesis and the anchorage-dependent and -independent growth of human colon carcinoma (LoVo), hepatoma (Mahlavu and PLC/PRF/5) and gastric carcinoma (KATO III). Both drugs severely inhibited DNA synthesis, cellular proliferation and Ras farnesylation in LoVo and moderately reduced them in Mahlavu and PLC/PRF/5 but not in KATO III. Complete sequencing of ras genes, however, revealed that LoVo and KATO III have activated Ki-ras and activated N-ras, respectively, whereas Mahlavu and PLC/PRF/5 have no activated ras. We next checked whether the inhibition of the cellular proliferation is due to the blocking of nuclear lamin function. Neither drug disturbed lamin farnesylation and localization, as demonstrated using metabolic labelling, immunoblotting and indirect immunofluorescence. These results indicate that manumycin and KT7595 can inhibit Ras farnesylation and cell growth without disturbing the farnesylation and localization of the lamins on human tumour cell lines. Images Figure 5 Figure 6 Figure 7 Figure 8 |
| اللغة: | English |
| تدمد: | 1532-1827 0007-0920 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a47fcab3a8257b799f429a460ecd8a96Test http://europepmc.org/articles/PMC2228099Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a47fcab3a8257b799f429a460ecd8a96 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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