Cryptophycin: A New Antimicrotubule Agent Active against Drug-resistant Cells

Charles Smith, Xinqun Zhang, Susan L. Mooberry, Gregory M.L. Patterson, Richard E. Moore

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

Cryptophycin is a cytotoxic dioxadiazacyclohexadecenetetrone isolated from cyanobacteria of the genus Nostoc. Incubation of L1210 leukemia cells with cryptophycin resulted in dose-dependent inhibition of cell proliferation in parallel with increases in the percentage of cells in mitosis (half-maximal effects at <10 pM). Indirect immunofluorescence studies demonstrated that treatment of A-10 vascular smooth muscle cells with cryptophycin results in marked depletion of cellular microtubules and reorganization of vimentin intermediate filaments, similar to the effects of vinblastine. Cytochalasin B caused the depolymerization of microfilaments in these cells, while neither vinblastine nor cryptophycin affected this cytoskeletal component Pretreatment of cells with taxol prevented microtubule depolymerization in response to either vinblastine or cryptophycin. While microtubule depolymerization in response to vinblastine was rapidly reversed by removal of the drug, cells treated with cryptophycin remained microtubule depleted for at least 24 h after removal of the compound. Combinational treatments with vinblastine and cryptophycin resulted in additive cytotoxicity. Ovarian carcinoma and breast carcinoma cells which are multiply drug resistant due to overexpression of P-glycoprotein are markedly less resistant to cryptophycin than they are to vinblastine, colchicine, and taxol. Therefore, cryptophycin is a new antimicrotubule compound which appears to be a poorer substrate for P-glycoprotein than are the Vinca alkaloids. This property may confer an advantage to cryptophycin in the chemotherapy of drug-resistant tumors.

Original languageEnglish (US)
Pages (from-to)3779-3784
Number of pages6
JournalCancer Research
Volume54
Issue number14
StatePublished - Jul 15 1994

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Vinblastine
Pharmaceutical Preparations
Microtubules
P-Glycoprotein
Paclitaxel
Nostoc
cryptophycin
Vinca Alkaloids
Leukemia L1210
Cytochalasin B
Intermediate Filaments
antineoplaston A10
Colchicine
Cyanobacteria
Vimentin
Cellular Structures
Indirect Fluorescent Antibody Technique
Actin Cytoskeleton
Vascular Smooth Muscle
Mitosis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Smith, C., Zhang, X., Mooberry, S. L., Patterson, G. M. L., & Moore, R. E. (1994). Cryptophycin: A New Antimicrotubule Agent Active against Drug-resistant Cells. Cancer Research, 54(14), 3779-3784.
Smith, Charles ; Zhang, Xinqun ; Mooberry, Susan L. ; Patterson, Gregory M.L. ; Moore, Richard E. / Cryptophycin : A New Antimicrotubule Agent Active against Drug-resistant Cells. In: Cancer Research. 1994 ; Vol. 54, No. 14. pp. 3779-3784.
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abstract = "Cryptophycin is a cytotoxic dioxadiazacyclohexadecenetetrone isolated from cyanobacteria of the genus Nostoc. Incubation of L1210 leukemia cells with cryptophycin resulted in dose-dependent inhibition of cell proliferation in parallel with increases in the percentage of cells in mitosis (half-maximal effects at <10 pM). Indirect immunofluorescence studies demonstrated that treatment of A-10 vascular smooth muscle cells with cryptophycin results in marked depletion of cellular microtubules and reorganization of vimentin intermediate filaments, similar to the effects of vinblastine. Cytochalasin B caused the depolymerization of microfilaments in these cells, while neither vinblastine nor cryptophycin affected this cytoskeletal component Pretreatment of cells with taxol prevented microtubule depolymerization in response to either vinblastine or cryptophycin. While microtubule depolymerization in response to vinblastine was rapidly reversed by removal of the drug, cells treated with cryptophycin remained microtubule depleted for at least 24 h after removal of the compound. Combinational treatments with vinblastine and cryptophycin resulted in additive cytotoxicity. Ovarian carcinoma and breast carcinoma cells which are multiply drug resistant due to overexpression of P-glycoprotein are markedly less resistant to cryptophycin than they are to vinblastine, colchicine, and taxol. Therefore, cryptophycin is a new antimicrotubule compound which appears to be a poorer substrate for P-glycoprotein than are the Vinca alkaloids. This property may confer an advantage to cryptophycin in the chemotherapy of drug-resistant tumors.",
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Smith, C, Zhang, X, Mooberry, SL, Patterson, GML & Moore, RE 1994, 'Cryptophycin: A New Antimicrotubule Agent Active against Drug-resistant Cells', Cancer Research, vol. 54, no. 14, pp. 3779-3784.

Cryptophycin : A New Antimicrotubule Agent Active against Drug-resistant Cells. / Smith, Charles; Zhang, Xinqun; Mooberry, Susan L.; Patterson, Gregory M.L.; Moore, Richard E.

In: Cancer Research, Vol. 54, No. 14, 15.07.1994, p. 3779-3784.

Research output: Contribution to journalArticle

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AU - Patterson, Gregory M.L.

AU - Moore, Richard E.

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N2 - Cryptophycin is a cytotoxic dioxadiazacyclohexadecenetetrone isolated from cyanobacteria of the genus Nostoc. Incubation of L1210 leukemia cells with cryptophycin resulted in dose-dependent inhibition of cell proliferation in parallel with increases in the percentage of cells in mitosis (half-maximal effects at <10 pM). Indirect immunofluorescence studies demonstrated that treatment of A-10 vascular smooth muscle cells with cryptophycin results in marked depletion of cellular microtubules and reorganization of vimentin intermediate filaments, similar to the effects of vinblastine. Cytochalasin B caused the depolymerization of microfilaments in these cells, while neither vinblastine nor cryptophycin affected this cytoskeletal component Pretreatment of cells with taxol prevented microtubule depolymerization in response to either vinblastine or cryptophycin. While microtubule depolymerization in response to vinblastine was rapidly reversed by removal of the drug, cells treated with cryptophycin remained microtubule depleted for at least 24 h after removal of the compound. Combinational treatments with vinblastine and cryptophycin resulted in additive cytotoxicity. Ovarian carcinoma and breast carcinoma cells which are multiply drug resistant due to overexpression of P-glycoprotein are markedly less resistant to cryptophycin than they are to vinblastine, colchicine, and taxol. Therefore, cryptophycin is a new antimicrotubule compound which appears to be a poorer substrate for P-glycoprotein than are the Vinca alkaloids. This property may confer an advantage to cryptophycin in the chemotherapy of drug-resistant tumors.

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Smith C, Zhang X, Mooberry SL, Patterson GML, Moore RE. Cryptophycin: A New Antimicrotubule Agent Active against Drug-resistant Cells. Cancer Research. 1994 Jul 15;54(14):3779-3784.