Paclitaxel and water-soluble poly (L-glutamic acid)-paclitaxel, induce direct chromosomal abnormalities and cell death in a murine metastatic melanoma cell line.
The purpose of this study was to demonstrate the effects of paclitaxel and water-soluble poly (L-glutamic acid)-paclitaxel (PG-TXL), on chromosome morphology, telomeric associations, and induction of cell death in a murine melanoma cell line (K-1735 clone X-21). Murine melanoma cells were treated with various concentrations (0.1 microgram, 1.0 microgram, 4.0 micrograms, and 8.0 micrograms/ml) of paclitaxel alone, PG alone, or PG-TXL for 2 hr and 4 hr and harvested immediately without recovery. We found that: (1) the frequency of metaphases with telomeric associations increased, (2) metaphases had clumped and distorted chromosome morphology, (3) cells accumulated in metaphase (mitotic arrest), and (4) cell death had been induced. Cells treated with PG-TXL showed more such abnormalities than did cells treated with either paclitaxel or PG alone. Our preliminary results indicate that PG-TXL may be superior to paclitaxel alone in inducing cytotoxic effects, and these effects could be mediated by various chromosomal abnormalities in cancer cells.
Multani
A S
AS
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Li
C
C
Ozen
M
M
Yadav
M
M
Yu
D F
DF
Wallace
S
S
Pathak
S
S
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002875:Chromosomes / Q000187:drug effects; D002999:Clone Cells; D007621:Karyotyping; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology; D008677:Metaphase; D051379:Mice; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000633:toxicity*; D011099:Polyglutamic Acid / Q000633:toxicity / Q000031:analogs & derivatives; D043823:Taxoids; D016615:Telomere / Q000187:drug effects; D014407:Tumor Cells, Cultured
D043823:Taxoids; D011099:Polyglutamic Acid; D017239:Paclitaxel; C509139:paclitaxel poliglumex