Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment
<p>Abstract</p> <p>Background</p> <p>Mutations within the tumor suppressor <it>TP53 </it>gene are one of the most common genetic alterations present at high frequency in human tumors and have been shown to be associated with resistance to radio-chemotherapy....
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| Format: | Article |
| Language: | English |
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BMC
2010-02-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/57 |
| _version_ | 1819030371051765760 |
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| author | Abolmaali Nasreddin D Tokalov Sergey V |
| author_facet | Abolmaali Nasreddin D Tokalov Sergey V |
| author_sort | Abolmaali Nasreddin D |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Mutations within the tumor suppressor <it>TP53 </it>gene are one of the most common genetic alterations present at high frequency in human tumors and have been shown to be associated with resistance to radio-chemotherapy. The lack of the wild type <it>TP53 </it>gene in cancer cells could be exploited for therapeutic advantage using a sequence of two antagonistic drugs. The aim of this study was to selectively kill p53 deficient cells (FaDu and H1299) by taxol and to protect p53 wild type cells (A549) by the prior administration of nutlin-3 in comparison to certain known anticancer drugs (5-fluorouracil, camptothecin, roscovitine).</p> <p>Methods</p> <p>Cytotoxic and cytostatic properties of 5-fluorouracil, camptothecin, roscovitine and nutlin-3 administrating alone or in combination with taxol were investigated in vitro by flow cytometry.</p> <p>Results</p> <p>It was found that nutlin-3 induced growth arrest and protected A549 cells from taxol. FaDu and H1299 cells responded to the same treatments with mitotic arrest and massive apoptosis. Other compounds (5-fluorouracil, camptothecin and roscovitine) revealed weaker selectivity and elevated toxicity in comparison to nutlin-3.</p> <p>Conclusions</p> <p>We propose a therapeutic strategy protecting normal cells from taxol while increasing apoptosis selectively in p53-deficient cells using nutlin-3.</p> |
| first_indexed | 2024-12-21T06:29:05Z |
| format | Article |
| id | doaj.art-6ee044686b9541608188fd7f4aacc6ac |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-21T06:29:05Z |
| publishDate | 2010-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6ee044686b9541608188fd7f4aacc6ac2022-12-21T19:13:02ZengBMCBMC Cancer1471-24072010-02-011015710.1186/1471-2407-10-57Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatmentAbolmaali Nasreddin DTokalov Sergey V<p>Abstract</p> <p>Background</p> <p>Mutations within the tumor suppressor <it>TP53 </it>gene are one of the most common genetic alterations present at high frequency in human tumors and have been shown to be associated with resistance to radio-chemotherapy. The lack of the wild type <it>TP53 </it>gene in cancer cells could be exploited for therapeutic advantage using a sequence of two antagonistic drugs. The aim of this study was to selectively kill p53 deficient cells (FaDu and H1299) by taxol and to protect p53 wild type cells (A549) by the prior administration of nutlin-3 in comparison to certain known anticancer drugs (5-fluorouracil, camptothecin, roscovitine).</p> <p>Methods</p> <p>Cytotoxic and cytostatic properties of 5-fluorouracil, camptothecin, roscovitine and nutlin-3 administrating alone or in combination with taxol were investigated in vitro by flow cytometry.</p> <p>Results</p> <p>It was found that nutlin-3 induced growth arrest and protected A549 cells from taxol. FaDu and H1299 cells responded to the same treatments with mitotic arrest and massive apoptosis. Other compounds (5-fluorouracil, camptothecin and roscovitine) revealed weaker selectivity and elevated toxicity in comparison to nutlin-3.</p> <p>Conclusions</p> <p>We propose a therapeutic strategy protecting normal cells from taxol while increasing apoptosis selectively in p53-deficient cells using nutlin-3.</p>http://www.biomedcentral.com/1471-2407/10/57 |
| spellingShingle | Abolmaali Nasreddin D Tokalov Sergey V Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment BMC Cancer |
| title | Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment |
| title_full | Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment |
| title_fullStr | Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment |
| title_full_unstemmed | Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment |
| title_short | Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment |
| title_sort | protection of p53 wild type cells from taxol by nutlin 3 in the combined lung cancer treatment |
| url | http://www.biomedcentral.com/1471-2407/10/57 |
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