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Lytic and sublytic effects of gossypol on red blood cells and thymocytes
Author(s) -
Chorieva Nargiza M.,
Fayziev Diyor D.,
Tsiferova Nargiza A.,
Toshtemirova Gulnoza A.,
Khamidova Ozoda J.,
Merzlyak Petr G.,
Kurbannazarova Ranokhon Sh.,
Ziyaev Khayrulla L.,
Gafurov Makhmud B.,
Sabirov Ravshan Z.
Publication year - 2021
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13429
Subject(s) - gossypol , chemistry , lysis , gramicidin , biophysics , hemolysis , osmotic shock , biochemistry , biology , membrane , immunology , gene
Gossypol is a natural polyphenol presently considered as a promising biological phytochemical with a range of activities including anticancer. We examined volume regulation‐dependent effects of gossypol using erythrocytes and thymic lymphocytes. Gossypol effectively lysed human red blood cells (RBC) with a half‐maximal concentration of 67.4 ± 1.6 μmol/L and in a non‐colloid osmotic manner. Sublytic gossypol doses of 1–10 μmol/L significantly protected RBC from osmotic hemolysis, but potentiated their sensitivity to the colloid‐osmotic lysis induced by a pore‐former nystatin. When added to the thymocytes suspension, gossypol caused a strong depression of the ability of cells to restore their volume under hypoosmotic stress with a half‐maximal activity at 2.1 ± 0.3 μmol/L. Gossypol suppressed regulatory volume decrease under experimental conditions, when cationic permeability was controlled by gramicidin D, and volume recovery depended mainly on anionic conductance, suggesting that the polyphenol inhibits the swelling‐induced anion permeability. In direct patch‐clamp experiments, gossypol inhibited the volume‐sensitive outwardly rectifying (VSOR) chloride channel in thymocytes and in human HCT116 and HeLa cells, possibly by a mechanism when gossypol molecule with a radius close to the size of channel pore plugs into the narrowest portion of the native VSOR chloride channel. Micromolar gossypol suppressed proliferation of thymocytes, HCT116 and HeLa cells. VSOR blockage may represent new mechanism of anticancer activity of gossypol in addition to its action as a BH3‐mimetic.