1-oleoyl-2-acetylglycerol and Endometrial-Neoplasms

The present study was undertaken to determine whether endometrial cancer cell line HEC-1-A differ from nontransformed cells, in that the cAMP and protein kinase C pathways may enhance IGF-I effects in mitogenesis by acting at the G1 phase of the cell cycle instead of G0. Immunofluorescence staining of HEC-1-A cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and flow cytometric analysis determined that HEC-1-A cells do not enter the G0 phase of the cell cycle when incubated in a serum-free medium. Approximately 51% of the cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to treatment. Forskolin and phorbol-12-myristate 13-acetate (PMA) were used to stimulate cAMP production and protein kinase C activity, respectively. IGF-I, forskolin and PMA each increased (P < 0.01) [3H]-thymidine incorporation in a dose and time dependent manner. The interaction of forskolin and PMA with IGF-I was then determined. Cells preincubated with forskolin or PMA followed by incubation with IFG-I incorporated significantly more (P < 0.01) [3H]-thymidine into DNA than controls or any treatment alone. It is concluded that forskolin and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to enhance IGF-I effects in cell proliferation.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adenocarcinoma; Colforsin; Culture Media, Serum-Free; Cyclic AMP; Diglycerides; Drug Interactions; Endometrial Neoplasms; Female; Flow Cytometry; Fluorescent Antibody Technique; G1 Phase; Humans; Insulin-Like Growth Factor I; Interphase; Phorbol Esters; Proliferating Cell Nuclear Antigen; Resting Phase, Cell Cycle; Signal Transduction; Thymidine; Tumor Cells, Cultured