| Autor: |
Kanno S; Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Japan. syu-kan@tohoku-pharm.ac.jp, Hiura T, Shouji A, Osanai Y, Ujibe M, Ishikawa M |
| Jazyk: |
angličtina |
| Zdroj: |
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2007 Nov; Vol. 30 (11), pp. 2069-74. |
| DOI: |
10.1248/bpb.30.2069 |
| Abstrakt: |
Cytosine arabinoside (1-beta-D-arabinofuranosylcytosine; Ara-C) is the most important antimetabolite used to induce remission in acute leukemia, but cellular resistance to Ara-C reflects a poor prognosis in cancer chemotherapy. To further investigate the mechanisms of resistance to Ara-C, we have established Ara-C-resistant NALM-6 cells. The activation of nuclear factor kappaB (NF-kappaB) was accompanied by the acquisition of Ara-C resistance. Telomerase activity has also increased with the acquisition of Ara-C resistance. The expression of Bid, Bax, or p53 proteins have been shown to increase correlated with the acquisition of Ara-C resistance. In contrast to the increase in these proteins, Bcl-2, Bcl-x, and Bag-1 proteins remained unchanged with the acquisition of Ara-C resistance. Fas expression increased with the acquisition of Ara-C resistance in the late stage. The induction of apoptosis and reduction of cell viability by cytotoxic anti-Fas antibody was more susceptible in resistant cells than parental cells. In conclusion, this report has shown that resistance to Ara-C up-regulates the activation of NF-kappaB, telomerase activity and Fas expression. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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