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Antimitotic and cytotoxic effects of theophylline in MDA-MB-231 human breast cancer cells.

Publication ,  Journal Article
Slotkin, TA; Seidler, FJ
Published in: Breast Cancer Res Treat
December 2000

A variety of cancer cell lines, including MDA-MB-231 human breast cancer cells, exhibit mitotic inhibition by cAMP. In earlier work, we found that the phosphodiesterase inhibitor, theophylline, reduced the number of cells and altered cellular morphology. In the current study, we evaluated the effects of theophylline on macromolecule synthesis and indices of cell viability. Theophylline evoked a concentration- and time-dependent decrease in DNA synthesis. However, the net decrease in cell number was greater than that predicted solely from mitotic arrest. Assessment of protein synthesis indicated a second effect of theophylline separable from that on DNA synthesis. This was confirmed by decreased cell viability and adhesion. Exposure of the cells to the phosphodiesterase inhibitor, IBMX, in concentrations that produced inhibition of DNA synthesis equivalent to that seen with theophylline, elicited a smaller reduction in cell number. Theophylline also evoked specific changes in the expression or function of membrane-bound adenylyl cyclase activity, effects that are likely to contribute to sustained reactivity of these cells to other cAMP-related inhibitors of cell proliferation, such as isoproterenol. The multiple pharmacologic properties of theophylline, producing mitotic inhibition, cytotoxicity and altered signaling in MDA-MB-231 cells, may provide insight into novel therapeutic strategies.

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Published In

Breast Cancer Res Treat

DOI

ISSN

0167-6806

Publication Date

December 2000

Volume

64

Issue

3

Start / End Page

259 / 267

Location

Netherlands

Related Subject Headings

  • Tumor Cells, Cultured
  • Time Factors
  • Theophylline
  • Phosphodiesterase Inhibitors
  • Oncology & Carcinogenesis
  • Mitosis
  • Humans
  • Female
  • Dose-Response Relationship, Drug
  • DNA Replication
 

Citation

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Slotkin, T. A., & Seidler, F. J. (2000). Antimitotic and cytotoxic effects of theophylline in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat, 64(3), 259–267. https://doi.org/10.1023/a:1026508605951
Slotkin, T. A., and F. J. Seidler. “Antimitotic and cytotoxic effects of theophylline in MDA-MB-231 human breast cancer cells.Breast Cancer Res Treat 64, no. 3 (December 2000): 259–67. https://doi.org/10.1023/a:1026508605951.
Slotkin TA, Seidler FJ. Antimitotic and cytotoxic effects of theophylline in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat. 2000 Dec;64(3):259–67.
Slotkin, T. A., and F. J. Seidler. “Antimitotic and cytotoxic effects of theophylline in MDA-MB-231 human breast cancer cells.Breast Cancer Res Treat, vol. 64, no. 3, Dec. 2000, pp. 259–67. Pubmed, doi:10.1023/a:1026508605951.
Slotkin TA, Seidler FJ. Antimitotic and cytotoxic effects of theophylline in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat. 2000 Dec;64(3):259–267.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

ISSN

0167-6806

Publication Date

December 2000

Volume

64

Issue

3

Start / End Page

259 / 267

Location

Netherlands

Related Subject Headings

  • Tumor Cells, Cultured
  • Time Factors
  • Theophylline
  • Phosphodiesterase Inhibitors
  • Oncology & Carcinogenesis
  • Mitosis
  • Humans
  • Female
  • Dose-Response Relationship, Drug
  • DNA Replication