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

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.

• Authors: K Irie, S Okuno, K Koshimizu, H Tokuda, H Nishino, A Iwashima
• Journal: International journal of cancer (Int J Cancer) Vol. 43 Issue 3 Pg. 513-9 (Mar 15 1989) ISSN: 0020-7136 [Print] United States
• PMID: 2538401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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