Abstract
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.
Highlights
Previous studies have revealed that different organic and aqueous extracts of Uncaria tomentosa, a Peruvian plant of the Rubiaceae family, contain biologically active substances, including immunostimulating pentacyclic oxindole alkaloids [1], ursane type pentacyclic triterpenes and quinovic acid glycosides, which were reported to possess anti-anti-inflammatory properties [2] and inhibit viral replication [3]
Plant extracts are extensively tested for anticancer activity, which may be a result of their antioxidant properties and apoptosis induction capacities, and in a future such extracts could be useful as an adjuvant treatment for cancer [2,16]
The present study showed that incubation of HepG2 cells with the water Uncaria tomentosa extract resulted in about 25%–30% reduction (* p < 0.05) of NF-κB activity water Uncaria tomentosa extract resulted in about 25%–30% reduction (* p < 0.05) of NF-κB activity (Figure 8), while in NHDF cells incubated with this extract about 16%–26% increase (* p < 0.05) in (Figure 8), while in NHDF cells incubated with this extract about 16%–26% increase (* p < 0.05) in activity was noted
Summary
Previous studies have revealed that different organic and aqueous extracts of Uncaria tomentosa, a Peruvian plant of the Rubiaceae family, contain biologically active substances, including immunostimulating pentacyclic oxindole alkaloids [1], ursane type pentacyclic triterpenes and quinovic acid glycosides, which were reported to possess anti-anti-inflammatory properties [2] and inhibit viral replication [3]. These extracts contained carboxyl alkyl esters, including quinic acid derivatives that, according to the available data, reduced proliferation of neoplastic cells and stimulated DNA repair [4], as well as antioxidants as catechin monomers and proanthocyanidins [5]. Ethyl acetate extract of Uncaria tomentosa in HL60 cells caused changes in mitochondrial membrane potential, release of cytochrome c to the cytosol and caspase-3 activation [8].
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