Resumen de Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica
The cytotoxic effect of different Colombian Piper plants was determined by the MTT assay in human cancer cell lines A549 (lung), PC-3 (prostate) and MDAMB-231 (breast). The most potent cytotoxic effect was found in the leaves ethanolic extract of P. eriopodon with IC50 values less than 25 μg/mL. After different chromatographic techniques, nine alkenylphenols (1 - 9) were isolated from the ethanolic extract of leaves from P. eriopodon and their molecular structures were identified by the analysis of the spectroscopic data (IR; NMR 1H, 13C 1D and 2D; HRESIMS), as well as by comparison of the spectral data with those reported in the literature. Of note, compounds 2, 3, 4, 5, 6, 7, 8 and 9 were reported for the first time. All isolated compounds showed cytotoxicity against the human cancer cell lines U373 (glioblastoma) and MCF7 (breast) with IC50 values in a range of 1.78 - 40.14 μg/mL. The higher cytotoxic effect of compounds 1, 2 and 3 was also shown by MTT assay using additional cancer cell lines A549 (lung), PC-3 (prostate) and non-tumourigenic HUVEC and human breast MCF10 cells. Compound 1 was the most potent inhibitor of human cancer cell viability, follow by compounds 2 and 1 respectively. Compounds 1 and 2 induced apoptosis through mitochondrial permeabilization and caspase activation while compound 3 acted on cell fate via caspase-independent/non-apoptotic mechanisms, likely involving mitochondrial dysfunctions and aberrant generation of reactive oxygen species (ROS). Finally, in silico modelling and molecular approaches suggested that all molecules inhibit XIAP by binding to XIAP-BIR3 domain. The results confirm the therapeutic potential of isolated compounds from P. eriopodon and demonstrates that XIAP is a key determinant of tumor control, at the molecular crossroad of caspase-dependent/independent cell death pathways.
