Inhibition of pinocytosis by hygrolidin family antibiotics: possible correlation with their selective effects on oncogene-expressed cells.
A fermentation broth of Streptomyces sp. SIPI-A4-0044 inhibited in vitro growth of src or ras oncogene-expressed (onc+) cells more strongly than that of oncogene-unexpressed (onc-) counterparts. The active components were isolated and identified as hygrolidin family antibiotics (HGL). In mixed cultures consisting of onc+ and onc- cells, at an appropriate ratio, HGL showed selective toxicity to focus like structures of onc+ cells, leaving monolayer areas of onc- cells little damaged. HGL rapidly inhibited pinocytosis, or the influx of neutral red into the cells, at concentrations partially inhibitory to the cell growth. In contrast, HGL only slightly inhibited the influx of 2-deoxyglucose, nucleosides and leucine and the syntheses of DNA, RNA and protein even at high concentrations. Upon prolonged exposure to sublethal concentrations of HGL, onc- cells but not onc+ cells recovered pinocytotic activity and resumed growth.
Suzukake-Tsuchiya
K
K
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Moriya
Y
Y
Kawai
H
H
Hori
M
M
Uehara
Y
Y
Iinuma
H
H
Naganawa
H
H
Takeuchi
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001358:Avian Sarcoma Viruses; D002460:Cell Line; D002461:Cell Line, Transformed; D007708:Kirsten murine sarcoma virus; D018942:Macrolides; D010873:Pinocytosis / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D018942:Macrolides; C068818:hygrolidin K1; C068817:hygrolidin K2