Creatine and phosphocreatine analogs: anticancer activity and enzymatic analysis.

Published

Journal Article

The brain isoform of creatine kinase has been implicated in cellular transformation processes. Cyclocreatine, a creatine kinase substrate analog, was previously shown to be cytotoxic to a broad spectrum of solid tumors. We have synthesized, enzymatically characterized, and evaluated the antitumor activity of a series of substrate analogs of creatine kinase. Using in vitro assays, we demonstrate that several of these analogs are cytotoxic to the human ME-180 cervical carcinoma, the MCF-7 breast adenocarcinoma and the HT-29 colon adenocarcinoma cell lines at low mM concentrations. Analogs that were active in vitro delayed the growth of a subcutaneously implanted rat 13,762 mammary adenocarcinoma. Tumor growth delays of 6-8 days were achieved, which is comparable to effects seen with standard regimens of currently used anticancer drugs. These studies further establish the creatine kinase system as a promising and novel target for anticancer chemotherapy drug design.

Full Text

Duke Authors

Cited Authors

  • Bergnes, G; Yuan, W; Khandekar, VS; O'Keefe, MM; Martin, KJ; Teicher, BA; Kaddurah-Daouk, R

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 8 / 3

Start / End Page

  • 121 - 130

PubMed ID

  • 8823808

Pubmed Central ID

  • 8823808

Electronic International Standard Serial Number (EISSN)

  • 1555-3906

International Standard Serial Number (ISSN)

  • 0965-0407

Language

  • eng