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- Title
Hyperthermic Enhancement of the Apoptotic and Antiproliferative Activities of Paclitaxel.
- Authors
Othman, Timothy; Goto, Shinji; Lee, Jeong-Beom; Taimura, Akihiro; Matsumoto, Takaaki; Kosaka, Mitsuo
- Abstract
The antineoplastic agent paclitaxel (PTX), a microtubule-stabilizing agent, is known to arrest cell cycle progression and induce apoptosis. Mild hyperthermia (HT) also disrupts the microtubule system and triggers apoptosis. We therefore investigated whether concurrent exposure of murine breast cancer cells to 10 μmol/l PTX and 43°C HT will promote improved anticancer effects. To do this, we exposed FM3A murine cancer cells to: (1) 10 μmol/l PTX for 1 h at 37°C followed by exposure at 43°C HT for 1 h; (2) 10 μmol/l PTX at 37°C for 2 h; (3) 37°C for 1 h followed by 43°C HT for 1 h, and (4) untreated cells at 37°C for 2 h which served as the control. Treatment No. 1 resulted in an enhanced cell cycle arrest, apoptosis and cytotoxicity. Exposure to 43°C HT alone or 10 μmol/l PTX alone induced lesser apoptosis and cytotoxicity than the two treatments concurrently applied. The apoptotic cell death occurred in a time-dependent manner as follows: (1) concurrently applied 43°C HT and 10 μmol/l PTX (5.6 ± 0.5, 16.5 ± 2 and 27.6 ± 1%); (2) 43°C HT alone (4.3 ± 1, 6.6 ± 0.3 and 12.7 ± 1%) and (3) 10 μmol/l PTX alone (4.4 ± 0.3, 8.6 ± 1 and 12.8 ± 1%) at 1, 6 and 24 h postexposure respectively compared to control of 2.0%. These data indicate that while both HT and PTX can individually induce apoptosis and antiproliferation in FM3A cancer cells, they may offer synergistic benefits when used concurrently.Copyright © 2001 S. Karger AG, Basel
- Subjects
ANTINEOPLASTIC agents; PACLITAXEL; MICROTUBULES; APOPTOSIS; EFFECT of temperature on toxicity
- Publication
Pharmacology, 2001, Vol 62, Issue 4, p208
- ISSN
0031-7012
- Publication type
Article
- DOI
10.1159/000056096