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 cultu...

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Published inJournal of antibiotics Vol. 44; no. 3; pp. 344 - 348
Main Authors SUZUKAKE-TSUCHIYA, KAYOKO, MORIYA, YUKARI, KAWAI, HIROYUKI, HORI, MAKOTO, UEHARA, YOSHIMASA, IINUMA, HIRONOBU, NAGANAWA, HIROSHI, TAKEUCHI, TOMIO
Format Journal Article
LanguageEnglish
Published Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1991
Japan Antibiotics Research Association
Subjects
Animals
Anti-Bacterial Agents - pharmacology
Antibiotics, Antineoplastic - pharmacology
Antineoplastic agents
Avian Sarcoma Viruses
Biological and medical sciences
Cell Line
Cell Line, Transformed
General aspects
Kirsten murine sarcoma virus
Macrolides
Medical sciences
Pharmacology. Drug treatments
Pinocytosis - drug effects
Streptomyces
Antineoplastic agent
Cell culture
Antibiotic
Analog
Animal
Pinocytosis
Gene expression
Onc gene
In vitro
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Summary: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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.44.344