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Cell cycle studies of cyclocreatine, a new anticancer agent.

Publication ,  Journal Article
Martin, KJ; Winslow, ER; Kaddurah-Daouk, R
Published in: Cancer Res
October 1, 1994

Cyclocreatine (CCr), a substrate analogue of creatine kinase (CK), exhibits antitumor activity in vitro and in vivo. To address its mechanism of action, we have examined its effects on tumor cell proliferation, viability, and cell cycle progression. Complete inhibition of proliferation of ME-180 cervical carcinoma cells was observed within 8 h of exposure to CCr and was characterized by an inhibition of progression out of all phases of the cell cycle. This initial effect was partially reversible on drug removal. Increased cytotoxicity was observed after several days of drug exposure and was most specific to cells in S. Previous studies have shown that CCr supports ATP regeneration through the CK system less efficiently than the natural substrate creatine and that CCr is active against tumor cell lines with elevated levels of CK. We propose here that the general inhibition of cell cycle progression reflects an effect of CCr on tumor cell energy availability through CK and that impaired energy homeostasis for several days leads to tumor cell death. Our results point out the unique nature of CCr as an anticancer agent that inhibits progression out of all phases of the cell cycle.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1994

Volume

54

Issue

19

Start / End Page

5160 / 5165

Location

United States

Related Subject Headings

  • Uterine Cervical Neoplasms
  • Tumor Cells, Cultured
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Humans
  • Female
  • Creatinine
  • Cell Survival
  • Cell Division
  • Cell Cycle
 

Citation

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MLA
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Martin, K. J., Winslow, E. R., & Kaddurah-Daouk, R. (1994). Cell cycle studies of cyclocreatine, a new anticancer agent. Cancer Res, 54(19), 5160–5165.
Martin, K. J., E. R. Winslow, and R. Kaddurah-Daouk. “Cell cycle studies of cyclocreatine, a new anticancer agent.Cancer Res 54, no. 19 (October 1, 1994): 5160–65.
Martin KJ, Winslow ER, Kaddurah-Daouk R. Cell cycle studies of cyclocreatine, a new anticancer agent. Cancer Res. 1994 Oct 1;54(19):5160–5.
Martin, K. J., et al. “Cell cycle studies of cyclocreatine, a new anticancer agent.Cancer Res, vol. 54, no. 19, Oct. 1994, pp. 5160–65.
Martin KJ, Winslow ER, Kaddurah-Daouk R. Cell cycle studies of cyclocreatine, a new anticancer agent. Cancer Res. 1994 Oct 1;54(19):5160–5165.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1994

Volume

54

Issue

19

Start / End Page

5160 / 5165

Location

United States

Related Subject Headings

  • Uterine Cervical Neoplasms
  • Tumor Cells, Cultured
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Humans
  • Female
  • Creatinine
  • Cell Survival
  • Cell Division
  • Cell Cycle