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Abstract
Introduction. Breast cancer (BC) is one of the leading causes of death among women worldwide.
Aim. To study the effects of a new indole alkaloid isolated from butterbur on cultures of permanent BC cell lines.
Materials and Methods. We studied the antiproliferative properties of a new plant-based compound isolated from butterbur and identified as an indole alkaloid (P1) in vitro on permanent cultures of BC cells: MDA-MB-453 (HER2+), BT-474 (luminal with HER2+ expression) and BT-20 (triple negative), as well as skin fibroblasts. The cell cultures were incubated with (P1), doxorubicin, or a combination of the two for 48 hours. 48 hours after exposure, we performed the MTT test, plotted the dose-response curve, and calculated the IC₅₀ value. The interaction between doxorubicin and (P1) was studied using SynergyFinderPlus software with Zero Interaction Potency (ZIP).
Results. Compound P1 demonstrated pronounced antiproliferative activity against MDA-MB-453, BT-474 and BT-20 cell cultures, with no significant differences observed between them. The IC50 values for compound (P1) were 39.7 ± 2.4 μmol/L for BT-20, 49.23 ± 5.2 μmol/L for BT-474 and 31.74 ± 3.8 μmol/L for MDA-MB-453. At the same time, the viability of all three cultures was statistically significantly lower under the action of the tested alkaloid than in normal fibroblast cultures. Slight synergism between the alkaloid (P1) and doxorubicin was observed in the BT-20 culture. In the other two cultures, however, the interaction between the two compounds was antagonistic, particularly at (P1) concentrations above 22 μmol/L. Even taking into account the correction for multiple comparisons, the average viability value in BC cultures was statistically significantly lower than in fibroblast cultures at compound (P1) concentrations of 22 μmol/L and 44 μmol/L, and in MDA-MB453 cultures at a concentration of 11 μmol/L.
Conclusion. A new indole alkaloid, isolated from butterbur, exhibits a cytostatic effect on various breast cancer cell cultures when exposed to concentrations above 22 μmol/L for 48 hours. Further studies could focus on the slight synergistic effect of the alkaloid (P1) with doxorubicin, which was observed in triple-negative BT-20 BC cell cultures, as well as the antagonistic effect obtained in other cultures. The alkaloid under study can be considered a promising compound with the potential to inhibit BC cells.
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