Induction of mitochondria-dependent apoptosis through the inhibition of mevalonate pathway in human breast cancer cells by YM529, a new third generation bisphosphonate
| Autor: | Kiyoshi Sawai, Junji Magae, Mitsuhiko Mizuta, Naruhiko Mizuta, Hisakazu Yamagishi, Hiroo Nakajima, Mie Tsuruga, Ikuya Fujiwara, Koichi Sakaguchi |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Farnesyl pyrophosphate Mevalonic Acid Apoptosis Breast Neoplasms Pharmacology chemistry.chemical_compound Polyisoprenyl Phosphates Prenylation Humans Cytotoxicity Antineoplastic Agents Alkylating Diphosphonates biology Chemistry Cytochrome c Imidazoles Mitochondria Oncology Cancer cell biology.protein Protein farnesylation Mevalonate pathway Drug Screening Assays Antitumor Sesquiterpenes Signal Transduction |
| Zdroj: | Cancer Letters. 253:89-96 |
| ISSN: | 0304-3835 |
| Popis: | YM529, a new third generation bisphosphonate, induced apoptosis of a human breast cancer cell line, MX-1. Cytotoxic activity of YM529 was more potent than that of incadronate. YM529 activated caspase-9, but not caspase-8, and induced the release of cytochrome c into cytosol. YM529 increased Bax expression and decreased Bcl-2 expression, while it did not induce caspase-8-dependent Bid truncation. Farnesyl pyrophosphate prevented YM529-mediated cytotoxicity. These results suggest that YM529 is a potent therapeutic agent for human breast cancers, activating the mitochondria-dependent apoptotic pathway through the inhibition of protein farnesylation. |
| Databáze: | OpenAIRE |
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