Inhibition of colon tumor cell growth by 8-chloro-cAMP is dependent upon its conversion to 8-chloro-adenosine

Anticancer Drugs. 1992 Oct;3(5):485-91. doi: 10.1097/00001813-199210000-00007.

Abstract

Recent interest in site-selective cAMP analogs has focused on the role of 8-chloro-adenosine (8-Cl-adenosine) in the inhibition of tumor cell growth by 8-chloro-cAMP (8-Cl-cAMP) (Van Lookeren Campagne, et al. Cancer Res 1991; 51: 1600-5). We have evaluated 8-Cl-cAMP and 8-Cl-adenosine for their growth inhibitory activity against two human colon adenocarcinoma cell lines, HCT116 and FET. Because these cell lines have been adapted to grow in chemically defined medium we were able to evaluate the effect of serum on 8-Cl-cAMP's growth inhibitory activity. In addition, cells grown in serum-free medium were tested for their sensitivity to 8-Cl-cAMP, serum-activated 8-Cl-cAMP and 8-Cl-adenosine. IC50 values, determined by measuring cell growth using a MTT colorimetric assay, showed that 'serum activation' of 8-Cl-cAMP was required to achieve inhibition of HCT116 (IC50 = 1.3 +/- 0.1 microM) and FET (IC50 = 2.0 +/- 0.1 microM) cell growth. IC50 values were not reached at the highest concentrations tested (IC50 > 500 microM) in the absence of serum, permitting us to conclude that 8-Cl-cAMP does not have growth inhibitory activity between 1.0 and 500 microM doses. HCT116 and FET cells grown in media containing serum and in the presence of 8-Cl-adenosine had IC50 values of 0.6 +/- 0.1 and 0.9 +/- 0.2 microM, respectively. HCT116 and FET cells grown in chemically defined medium containing 8-Cl-adenosine exhibited IC50 values of 1.0 +/- 0.1 and 3.1 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Chloroadenosine / analogs & derivatives*
  • 2-Chloroadenosine / pharmacokinetics
  • 2-Chloroadenosine / pharmacology
  • 8-Bromo Cyclic Adenosine Monophosphate / analogs & derivatives*
  • 8-Bromo Cyclic Adenosine Monophosphate / blood
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacokinetics
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Biotransformation
  • Blood
  • Cell Division / drug effects
  • Chromatography, High Pressure Liquid
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Culture Media
  • Drug Resistance
  • Drug Screening Assays, Antitumor
  • Humans
  • Prodrugs / pharmacokinetics*
  • Tumor Cells, Cultured / drug effects

Substances

  • Culture Media
  • Prodrugs
  • 2-Chloroadenosine
  • 8-Bromo Cyclic Adenosine Monophosphate
  • 8-chloro-cyclic adenosine monophosphate
  • 8-chloroadenosine