Indomethacin and telomerase activity in tumor growth retardation

It is well-recognized that cycloogygenase inhibitors attenuate tumor growth in tumor models, although underlying mechanisms are unclear. In the presen t study we report that indomethacin retards MCG-101 tumor growth on mice by induction of apoptosis/necrosis and inhibits telomere elongation. The inhi bition of telomerase activity by NSAIDs (indomethacin, mobic, sulindac sulf one, suramin) was, however, not a universal finding, since a mouse melanoma (K1735-M2) did not respond. By contrast, a human cell line of colon carcin oma origin (HT-29), responded by both retarded growth and telomerase activi ty despite a low intrinsic production of prostaglandins, mainly PGE(2). The refore, it is not likely that indomethacin inhibition of tumor growth and t elomere elongation is directly related to Cox-1/Cox-2 activities in tumor c ells. Also, NSAIDs at 25 muM (sulindac sulfone) decreased growth and telome rase activity in MCG-101 cells, without any effects on PGE(2) production, w hile ibuprofen reduced PGE(2) production but had no effect on growth or tel omerase activity. Our results demonstrate that cyclooxygenase inhibitors ca n retard tumor growth both in murine tumors and in human tumor cells by inh ibition of telomerase activity in addition to previously recognized mechani sms as induction of apoptosis, inhibition of cell proliferation, influence on the expression of growth factors around growing tumors and attenuation o f neoangiogenesis.