Biological activities and cellular uptake studies of fluorescent derivatives of indole alkaloid tumor promoter teleocidin

Int J Cancer. 1989 Mar 15;43(3):513-9. doi: 10.1002/ijc.2910430329.

Abstract

To investigate the interaction between tumor promoters and their cellular targets, 6 new fluorescent derivatives of indole alkaloid tumor promoter teleocidin were synthesized from (-)-indolactam V, and examined for induction of Epstein-Barr virus, binding ability to the TPA receptor on mouse skin and activation of protein kinase C. (-)-7-(2-N-Dansylaminoethyl)indolactam V (dansyl-ILV) had strong activities and proved to be a potent tumor promoter in a 2-stage carcinogenesis experiment. (-)-2-Formyl-7-decanoyl-indolactam V (FD-ILV) showed a weak but significant activity. The other 4 derivatives had little activity. Treatment of HeLa cells with dansyl-ILV and FD-ILV resulted in intense fluorescence in the entire cytoplasm and on the nuclear membrane. Inactive or less active derivatives with hydrophobicity similar to that of dansyl-ILV showed significant cytoplasmic fluorescence, and those far less hydrophobic than dansyl-ILV or far more hydrophobic than FD-ILV showed little fluorescence. This suggested that hydrophobicity rather than biological activity determines the cellular uptake of these fluorescent probes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / biosynthesis
  • Caenorhabditis elegans Proteins*
  • Carcinogens* / chemical synthesis
  • Carcinogens* / pharmacokinetics
  • Carrier Proteins
  • Chemical Phenomena
  • Chemistry, Physical
  • Enzyme Activation / drug effects
  • Female
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / pharmacokinetics*
  • Fluorescent Dyes / pharmacology
  • HeLa Cells / metabolism
  • Herpesvirus 4, Human / immunology
  • Humans
  • Lyngbya Toxins / chemical synthesis
  • Lyngbya Toxins / pharmacokinetics*
  • Lyngbya Toxins / pharmacology
  • Mice
  • Protein Kinase C / metabolism
  • Receptors, Drug / drug effects
  • Receptors, Drug / metabolism
  • Skin Neoplasms / chemically induced
  • Tetradecanoylphorbol Acetate / metabolism

Substances

  • Antigens, Viral
  • Caenorhabditis elegans Proteins
  • Carcinogens
  • Carrier Proteins
  • Epstein-Barr virus early antigen
  • Fluorescent Dyes
  • Lyngbya Toxins
  • Receptors, Drug
  • phorbol ester binding protein
  • phorbol ester receptor
  • teleocidins
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate