Differential effects of taxol on two human cancer cell lines.
Taxol is the prototype of a new class of drugs with promise in the treatment of various cancers. Its mechanism of action is not fully understood. We have investigated the effects of taxol on two human cancer cell lines, HT-29, derived from a colon carcinoma, and SK-MEL-28, from a melanoma. Immunofluorescence staining for microtubules, cell cycle analysis by flow cytometry, cytotoxicity assays, and DNA fragmentation studies by agarose gel electrophoresis were performed. The two cell lines responded quite differently to taxol. HT-29 cells, when treated with taxol for 24 h, showed an abundance of multiple microtubule asters and the cells were arrested in mitosis. Flow cytometry also showed arrest in mitosis and development of a hypodiploid region with increasing taxol incubation times. These cells were more sensitive to taxol exposure, which caused internucleosomal DNA fragmentation, indicative of apoptosis. The SK-MEL-28 cells, on the other hand, were less sensitive to taxol. Significant cytotoxic effects were only visible after 72 h. These cells exhibited a predominance of microtubule bundles and multinuclei, and only a few cells were arrested in mitosis. Flow cytometry revealed that the SK-MEL-28 cells became polyploid, as a result of exit from mitosis without cell division. These results suggest that the mechanism involved in taxol-induced cell death is different in these two cell lines.
Banerjee
S
S
Department of Biology, University of Ottawa, Ontario, Canada.
Fallis
A G
AG
Brown
D L
DL
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D019073:HT29 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008870:Microtubules / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D017239:Paclitaxel