Gossypol effects on endothelial cells and tumor blood flow

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Life Sciences; (United States)

DOI:https://doi.org/10.1016/0024-3205(91)90178-E· OSTI ID:5907276

Benz, C C; Iyer, S B; Asgari, H S; Matlin, S A; Aronson, F R ^[1]; Barchowsky, A ^[2]

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1. Univ. of California, San Francisco (United States)
2. Thomas Jefferson Univ., Philadelphia, PA (United States)

Isomers (-,+) of the antitumor agent gossypol (G) were studied for their ability to reduce tumor ATP and blood flow in rats bearing subcutaneously implanted pancreatic tumors. A 50% reduction in tumor ATP/Pi within 1h of a single injection of -G was associated with a 60% decline in tumor blood flow. To determine if these changes in tumor physiology could be due to a direct drug effect on tumor endothelium, G isomers were compared for their ability to alter protein ({sup 125}1-BSA) permeability and metabolic ({sup 32}P) labelling of cultured endothelial cells. Treatments for 1h produced no endothelial cell leakage, but 24h exposures to either -G or +G produced complete permeability of the monolayers to {sup 125}1-BSA. In contrast, 0.5-1.0h exposures to -G or +G produced 2 to 3-fold increases in phosphorylated 27kDa heat-shock protein, hsp-27. Hsp-27 phosphoprotein isoforms were differentially labelled following -G and +G exposures with the phosphorylation profile of -G appearing most similar to that of oxyradical producing agents known to induce hsp-27 and injure endothelial cells. The authors postulate that the tumor ischemic effects of -G are mediated by endothelial response to oxyradical production in a mechanism similar to that of tissue ischemia-reperfusion injury.

• OSTI ID: 5907276
• Journal Information: Life Sciences; (United States), Vol. 49:12; ISSN 0024-3205
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
NEOPLASMS
BLOOD FLOW
PANCREAS
ATP
ENDOTHELIUM
INHIBITION
IODINE 125
PHOSPHOPROTEINS
PHOSPHORUS 32
RATS
TRACER TECHNIQUES
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE GLANDS
GLANDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
RODENTS
TISSUES
VERTEBRATES
550901* - Pathology- Tracer Techniques