In Vitro Modulation of P-Glycoprotein Activity by <i>Euphorbia intisy</i> Essential Oil on Acute Myeloid Leukemia Cell Line HL-60R
<i>Euphorbia</i> species have a large spectrum of traditional medicinal uses. We tested the biological activities of the essential oil (EO) of <i>Euphorbia intisy</i> Drake in an acquired multidrug resistance leukemia model to assess whether the EO obtained by hydrodistillati...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2021-01-01T00:00:00Z.
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| Summary: | <i>Euphorbia</i> species have a large spectrum of traditional medicinal uses. We tested the biological activities of the essential oil (EO) of <i>Euphorbia intisy</i> Drake in an acquired multidrug resistance leukemia model to assess whether the EO obtained by hydrodistillation of stems was able to reverse the resistant phenotype. HL-60R cell lines are characterized by the overexpression of P-glycoprotein (P-gp), inhibitors of apoptosis proteins (IAPs) and constitutive expression of NF-κB. EO chemical composition was determined by GC/MS analysis; cytotoxic activity of EO by MTS assay alone or in combination with doxorubicin; pro-apoptotic effect and doxorubicin accumulation were analyzed by flow cytometry; P-gp ATPase activity was measured by P-gp-Glo™ assay systems kit. The ability to inhibit NF-κB and its target genes was also assessed. <i>E. intisy</i> EO exhibited a comparable cytotoxic effect and ability to block P-gp in both the HL-60 and its MDR variant HL-60R. In addition, EO suppressed P-gp protein expression and significantly downregulated MDR1 mRNA level, as well as some IAPs proteins, probably through the inhibition of NF-κB. Our results suggest that <i>E. intisy</i> EO could reverse P-gp-mediated drug resistance in tumor cells acting as a chemosensitizing agent. |
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| Item Description: | 10.3390/ph14020111 1424-8247 |