Unknown

LPA can function as a mitogen or an antimitogen, depending on the cell type and the receptors it expresses. It was tested 10 uM GRI977143 for its effect on cell proliferation of vector-transduced and LPA2-transduced MEF cells. LPA had no significant effect on the proliferation of empty vector-transduced MEF cells. Likewise, GRI977143 did not cause a significant increase in vector cell proliferation except at 72 h (p < 0.05). GRI977143 (10 μM) decreased caspase 9 activation in LPA2-transduced MEF cells by 46 ± 4%; this decrease was similar in its magnitude to that of 1 μM LPA, whereas 1 μM OTP resulted in a slightly smaller 38 ± 1% decrease. GRI977143 did not affect caspase 9 activation in the vector-transduced cells, whereas LPA and OTP even at a 1 μM concentration reduced caspase 9 activation by 20 to 24% . To guide our dosing considerations in the apoptosis assays, we also tested the dose-response relationship of our test compounds on doxorubicin-induced caspase 3 and 7 activation in vector- and LPA2-transduced MEF cells. In the LPA2-transduced MEF cells, GRI977143 elicited a dose-dependent and significant protection at ≥3 μM.