Taxotere inhibits in-vitro growth of human colonic cancer cell lines.
Taxotere a semisynthetic analogue of taxol, is prepared from a precursor extracted from needles of the tree, Taxus baccata. It is a mitotic spindle poison more potent than taxol, that increases the rate of microtubule assembly and inhibits depolymerization of microtubules. There has been little research on its effects on colorectal cancer. Five colorectal tumour cell lines were investigated using three modes: flow cytometry (to determine how Taxotere affects the cell cycle), MTT assay, (to examine the cytotoxicity of the drug), and measurement of tritiated thymidine uptake, (to see whether Taxotere affects the rate of DNA synthesis and cell turnover). A time-course experiment, using flow cytometry, showed effects beginning between 0 and 2 hours after exposure. 24-hour assays were conducted for flow cytometry, and showed large changes, arresting most cells in G2/M phases (e.g., cell line LIM 1215 exposed to 1 x 10(-6) M Taxotere showed 72% of cells in G2/M compared to 14.7% in controls). 24 and 48 hour assays were conducted for MTT and measurement of tritiated thymidine uptake. MTT showed significant inhibitory effects, with maximum inhibitions varying between 5 and 70% for different cell lines after 48 hours (P < 0.05), while uptake of tritiated thymidine was not altered. While Taxotere has dose-limited toxicity, our results suggest that many human colonic cancers will be sensitive to Taxotere.
Karantanis
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Department of Surgery, University of New South Wales, St George Hospital, Kogarah, Sydney, Australia.
Nicholson
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Morris
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D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004273:DNA, Neoplasm / Q000187:drug effects; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D043823:Taxoids; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel