Biological activities and cellular uptake studies of fluorescent derivatives of indole alkaloid tumor promoter teleocidin.
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.
Irie
K
K
Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan.
Okuno
S
S
Koshimizu
K
K
Tokuda
H
H
Nishino
H
H
Iwashima
A
A
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002352:Carrier Proteins; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D006367:HeLa Cells / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008235:Lyngbya Toxins / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D000956:Antigens, Viral; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; C033305:Epstein-Barr virus early antigen; D005456:Fluorescent Dyes; D008235:Lyngbya Toxins; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C022176:teleocidins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate