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Planta Med 2014; 80(13): 1088-1096
DOI: 10.1055/s-0034-1382993
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs

Jelena Dinić
1   Institute for Biological Research, Department of Neurobiology, University of Belgrade, Belgrade, Serbia
,
Miroslav Novaković
2   Institute for Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
,
Ana Podolski-Renić
1   Institute for Biological Research, Department of Neurobiology, University of Belgrade, Belgrade, Serbia
,
Sonja Stojković
1   Institute for Biological Research, Department of Neurobiology, University of Belgrade, Belgrade, Serbia
,
Boris Mandić
3   Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
,
Vele Tešević
3   Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
,
Vlatka Vajs
2   Institute for Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
,
Aleksandra Isaković
4   Faculty of Medicine, University of Belgrade, Belgrade, Serbia
,
Milica Pešić
1   Institute for Biological Research, Department of Neurobiology, University of Belgrade, Belgrade, Serbia
› Author Affiliations
Further Information

Publication History

received 13 April 2014
revised 03 July 2014

accepted 23 July 2014

Publication Date:
19 August 2014 (online)

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Abstract

Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI–H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1α was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1α). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.

Key words

diarylheptanoid - Alnus glutinosa - Betulaceae - curcumin - doxorubicin - cisplatin - reactive oxygen species (ROS)

Supporting Information

 

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