alpha-Trinositol inhibits FGF-stimulated growth of smooth muscle and breast cancer cells.
alpha-Trinositol (d-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP(3), has been studied for its anti-inflammatory and other effects in animal experiments and in human. The mechanisms of action remain unknown. Several human pathologies are associated with uncontrolled production of fibroblast growth factors (FGFs). FGF-2 induces vascular smooth muscle cell proliferation, which contributes to restenosis after coronary balloon angioplasty. The expression of several FGFs is also increased in tumors. We studied the effects of the water- and lipid-soluble derivatives of alpha-trinositol on the FGF-2- and/or FGF-8-induced proliferation of human pulmonary artery smooth muscle cells (HPASMC) and S115 mouse breast cancer cells. alpha-Trinositol decreased the FGF-mediated proliferation of HPASMC and S115 cells. Membrane permeability did not seem obligatory since the lipid-soluble form of alpha-trinositol was less effective than the water-soluble derivative. These results suggest a new biological function for certain phosphoinositides in the modulation of FGF-regulated processes.
Sirén
Matti J
MJ
JGK Memorial Research Laboratory and Library, Helsinki, Finland.
Vainiomäki
Maija
M
Väänänen
Kalervo
K
Härkönen
Pirkko
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000254:growth & development*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D007295:Inositol Phosphates; C059368:atrinositol