摘要:
The aim of this diploma thesis was to investigate the anti-neoplastic potential of two healing plants,who were already used by the Maya of the Guatemala/Belize area against severe inflammatory conditions such as neuritis, rheumatism, arthritis, coughs, bruises and tumours. S. podophyllum and Pluchea odorata were collected, dried, and extracted with five solvents of increasing polarity. To rule out the possibility, that the different solvent types contain non-specific toxic components we compared different extracts prepared from L. sativa var. capitata, the green "iceberg" salad. The inhibition of proliferation and the induction of cell death were investigated in HL-60 and MCF-7 cells, because these are endpoints to measure the efficiency of anti-cancer drugs. Western blot and FACS analyses aimed to obtain data on the underlying mechanisms. While extracts of S. podophyllum showed only moderate anti-cancer activity and were therefore not further investigated, particularly the dichloromethane extract of P. odorata inhibited the cell cycle in G2-M which correlated with the activation of checkpoint kinase 2, and the down-regulation of Cdc25A and cyclin D1 as well as the inactivation of Erk1/2. This extract was an extraordinarily strong inducer of HL-60 and MCF-7 cell death activating caspase 3 followed by PARP signature type cleavage. The initiating death trigger was likely the stabilization of microtubules monitored by the rapid acetylation of α-tubulin, which was even more pronounced than that triggered by taxol. L. sativa water extract showed a distinct antiproliferative effect in HL-60 and MCF-7 cells. It works in a similar way than P. odorata. Chk2 was activated which was paralelled by Cyclin D downregulation and p21 upregulation. Additionally, Erk1/2 was phosphorylated and therefore mitotic signaling was in conflict with p21 downregulation. Furthermore the water- and the ethyl acetates extract triggered apoptosis in HL-60 cells, while the extracts had no effect in MCF-7 cells.
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