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DOI: 10.1055/s-2004-819235
Modulation of the expression of angiogenic growth factors by mistletoe extracts and selenium
Objectives: Angiogenesis plays a crucial role during the formation of the Corpus luteum, in cancer growth, and wound healing. It is differentially regulated by various growth factors of which the Vascular Endothelial Growth Factor (VEGF)- and the angiopoietin (ANGPT)-family are the most prominent. Recent data suggests that mistletoe extracts and selenium might modulate angiogenic processes. Here we report about the influence of these substances on the expression of angiogenic growth factors in human granulosa cells (GC).
Methods: GC were isolated from follicular fluid of patients undergoing IVF therapy as described elsewhere (Keck et al., 1998). After preincubation, cells were stimulated with different dilutions of a mistletoe extract (0.33 to 33.3µg/ml) and selenium (0,0166 to 16.66µg/ml). After 20 hours RNA was isolated by standard methods and mRNA expression of following factors was determined by RT-PCR: ANGPT1, ANGPT2, VEGF-A, VEGF-B. The results of ANGPT2 and VEGF mRNA expression were validated by Real Time PCR.
Results: The present results demonstrate that the expression of ANGPT2 in GC is significantly decreased after incubation of GC with 1.66µg/ml of selenium. Other dilutions have no significant effect. Whereas a dose of 16,6µg/ml leads to cell death. In contrast to ANGPT2, the expression of ANGPT1, VEGF-A and VEGF-B is not significantly influenced by selenium. Application of 0.33µg/ml mistletoe extracts decreased the expression of VEGF-A but had no effect on other genes investigated.
Conclusions: Our findings indicate that the reported angiogenic effects of selenium and mistletoe extracts may be transmitted via VEGF-A and ANGPT2 dependent pathways. In contrast to previous data in cancer cell lines we did not detect a change of expression of VEGF-A after application of selenium. This finding might reflect differences between cancer cell lines and primary GC. The dose dependent effect of mistletoe extract on the expression of VEGF might help to explain previous reports about antiangiogenic effects of mistletoe therapy in cancer patients.