Abstract | PURPOSE: METHODS: Antiproliferative effects of cryptophycin 52 were measured indirectly by detection of the metabolic reduction of alamarBlue. Cytoxicity was assessed by enzymatic dye activation ( calcein AM) combined with dye exclusion ( ethidium homodimer) and by clonogenicity assay. Cell cycle effects were evaluated using flow cytometry and fluorescence microscopy. RESULTS: Both antiproliferative and cytotoxic effects of cryptophycin 52 were concentration- and time-dependent. IC50 values for antiproliferative activity in both solid and hematologic tumor cell lines were in the low picomolar range, and without exception, were significantly below values for the antimitotic agents paclitaxel and vinblastine. Flow cytometry and microscopic examination of tumor cells treated with cryptophycin 52 indicated that they accumulated in the mitotic phase of the cell cycle. Cryptophycin 52 was tested for its sensitivity to multidrug-resistance in several paired cell lines in which a sensitive parental line was matched with a multidrug-resistant derivative line. The resistant lines have been shown to over express Pgp and/or MRP multidrug-resistance transport factors. Compared to other antimitotic agents ( paclitaxel, vinblastine, vincristine), the potency of cryptophycin 52 was shown to be minimally affected in multidrug-resistant cells compared to their sensitive parental lines. CONCLUSION:
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Authors | M M Wagner, D C Paul, C Shih, M A Jordan, L Wilson, D C Williams |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 43
Issue 2
Pg. 115-25
( 1999)
ISSN: 0344-5704 [Print] Germany |
PMID | 9923816
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Depsipeptides
- Lactams
- Lactones
- cryptophycin 52
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Topics |
- Antineoplastic Agents
(chemistry, pharmacology, toxicity)
- Cell Cycle
(drug effects)
- Cell Division
(drug effects)
- Colony-Forming Units Assay
- Depsipeptides
- Dose-Response Relationship, Drug
- Drug Resistance, Multiple
- Flow Cytometry
- Humans
- Lactams
(chemistry, pharmacology, toxicity)
- Lactones
(chemistry, pharmacology, toxicity)
- Microscopy, Fluorescence
- Molecular Structure
- Tumor Cells, Cultured
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