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Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity

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Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy with the Laboratory Medicine Division, and Center for Preclinical Studies, Medical University of Warsaw, 02097 Warsaw, Poland
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Department of Clinical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, 02097 Warsaw, Poland
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Department of Molecular Plant Physiology, Faculty of Biology, University of Warsaw, 02096 Warsaw, Poland
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Institute of Bioorganic Chemistry Polish Academy of Science, Poznań, 61704 Poznań, Poland
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Chair and Department of Pharmaceutical Botany, Medical University of Lublin, 20093 Lublin, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Thomas J. Schmidt
Molecules 2017, 22(4), 620; https://doi.org/10.3390/molecules22040620
Received: 20 February 2017 / Revised: 7 April 2017 / Accepted: 8 April 2017 / Published: 12 April 2017
(This article belongs to the Section Natural Products Chemistry)
Uncaria tomentosa is a woody vine with a long history of use in traditional Peruvian medicine and nowadays supplements containing this vine as ingredient are available. Immunomodulating, anti-inflammatory and anticancer properties of Uncaria tomentosa have been suggested and attributed mainly to the presence of tetracyclic or pentacyclic oxindole alkaloids. However, the synergic action of different compounds occurring in extracts and modulation of redox processes may significantly influence the anticancer activity of Uncaria tomentosa. The aim of the present study was to investigate for the first time the cytotoxic effects of the tetracyclic alkaloids free aqueous extract (decoction) of dried Uncaria tomentosa leaf blades in normal and cancer cells, and to assess the effect of the tested extract on cisplatin (CDDP) cytotoxicity. Tested Uncaria tomentosa extract was not cytotoxic for NHDF cells, but demonstrated cytotoxic effect against HepG2 cells. The extract increased ROS production in HepG2 cells, which resulted in decreased GSH level, leading to apoptosis of these cells through activation of caspase-3 and caspase-7. A reduction of NF-κB active form was observed in cancer cells. In normal cells the extract did not affect ROS production, GSH level and NF-κB activity, and maintained cell viability. HepG2 cells incubation with Uncaria tomentosa decoction and simultaneously with CDDP resulted in an increase in CDPP cytotoxic activity against HepG2, while under the same conditions Uncaria tomentosa prevents NHDF cell viability reduction due to CDDP. The results indicate that Uncaria tomentosa leaves decoction modulates differently cancer and normal cells oxidative metabolism and, enhanced cytotoxicity of CDDP against cancer cells and at the same time increased normal healthy cells resistance to cisplatin. Further studies are needed to confirm our observations and to describe underlying molecular mechanism, and the potential usefulness of Uncaria tomentosa decoction in adjuvant therapy for cancer. View Full-Text
Keywords: Uncaria tomentosa decoction; tannin and alkaloids; HepG2 cells; ROS production; NF-κB activity; CDDP cytotoxicity Uncaria tomentosa decoction; tannin and alkaloids; HepG2 cells; ROS production; NF-κB activity; CDDP cytotoxicity
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Kośmider, A.; Czepielewska, E.; Kuraś, M.; Gulewicz, K.; Pietrzak, W.; Nowak, R.; Nowicka, G. Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity. Molecules 2017, 22, 620.

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