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Molecules 2015, 20(8), 15343-15358; doi:10.3390/molecules200815343

The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells

1
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, Hradec Králové CZ-500 05, Czech Republic
2
Department of Medical Biology and Genetics, Faculty of Medicine, Charles University in Prague, Šimkova 870, Hradec Králové CZ-500 38, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 9 July 2015 / Revised: 6 August 2015 / Accepted: 13 August 2015 / Published: 21 August 2015
(This article belongs to the Collection Herbal Medicine Research)
View Full-Text   |   Download PDF [1161 KB, uploaded 21 August 2015]   |  

Abstract

The sesquiterpenes β-caryophyllene, β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER), and valencene (VAL) are substantial components of the essential oil from Myrica rubra leaves which has exhibited significant antiproliferative effects in several intestinal cancer cell lines, with CaCo-2 cells being the most sensitive. The present study was designed to evaluate the effects of these sesquiterpenes on the efficacy and toxicity of the anticancer drug doxorubicin (DOX) in CaCo-2 cancer cells and in primary culture of rat hepatocytes. Our results showed that HUM, NER, VAL and CAO inhibited proliferation of CaCo-2 cancer cells but they did not affect the viability of hepatocytes. CAO, NER and VAL synergistically potentiated the efficacy of DOX in cancer cells killing. All sesquiterpenes exhibited the ability to selectively increase DOX accumulation in cancer cells and did not affect DOX concentration in hepatocytes. Additionally, CAO and VAL were able to increase the pro-oxidative effect of DOX in CaCo-2 cells. Moreover, CAO mildly ameliorated DOX toxicity in hepatocytes. Based on all results, CAO seems to be the most promising compound for further testing. View Full-Text
Keywords: terpenes; cytotoxicity; Myrica rubra; antiproliferative effect; drugs combinations terpenes; cytotoxicity; Myrica rubra; antiproliferative effect; drugs combinations
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ambrož, M.; Boušová, I.; Skarka, A.; Hanušová, V.; Králová, V.; Matoušková, P.; Szotáková, B.; Skálová, L. The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells. Molecules 2015, 20, 15343-15358.

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