Abstract
BackgroundAlizarin and purpurin are di- and trihydroxyanthraquinones derived from Rubia tinctorum L. Previous pharmacological studies have demonstrated that they exhibit certain degree of selective inhibitory effects towards cancer cells suggesting their application as a targeted drug for cancer. Our present work was aimed to investigate the suitability of hydroxyanthraquinones of Rubia tinctorum L. for targeted tumor therapy. The effects of alizarin, purpurin and an aqueous extract from transformed hairy root culture of Rubia tinctorum L. were examined on (1) cell proliferation, (2) apoptosis, (3) cell adhesion/morphology and (4) migration (chemotaxis, chemokinesis) of human melanoma cell lines (A2058, HT168-M1) and human fibroblast cells (MRC-5), as well as (5) the aqueous extract was analytically characterized.MethodsThe aqueous extract was prepared from R. tinctorum hairy root culture and qualitatively analyzed by HPLC and ESI–MS methods. The cell growth inhibitory activity of anthraquinones was evaluated by MTT-assay and by flow cytometry. The effect of anthraquinones on cell adhesion was measured by an impedance based technique, the xCELLigence SP. For the chemotaxis assay NeuroProbe® chamber was used. Computer based holographic microscopy was applied to analyze chemokinetic responses as well as morphometry. Statistical significance was determined by the one-way ANOVA test.ResultsIn the aqueous extract, munjistin (Mr = 284, tR = 18.4 min) as a principal component and three minor anthraquinones (pseudopurpurin, rubiadin and nordamnacanthal) were identified. The purpurin elicited a stronger but not apoptosis-mediated antitumor effect in melanoma cells (A2058: 10−6–10−5 M: 90.6–64.1 %) than in normal fibroblasts (10−6–10−5 M: 97.6–84.8 %). The aqueous extract in equimolar concentrations showed the most potent cytotoxicity after 72 h incubation (A2058: 10−6–10−5 M: 87.4–55.0 %). All tested substances elicited chemorepellent effect in melanoma cells, while in MRC-5 fibroblasts, only the alizarin exhibited such a repellent character. Indices of chemokinesis measured by holographic microscopy (migration, migration directness, motility and motility speed) were significantly enhanced by alizarin and purpurin as well, while morphometric changes were weak in the two melanoma cell lines.ConclusionsOur results highlight the effective and selective inhibitory activity of purpurin towards melanoma cells and its possible use as a targeted anticancer agent. The anthraquinones of the cytotoxic extract are suggested to apply in drug delivery systems as an anticancer drug.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-015-0271-4) contains supplementary material, which is available to authorized users.
Highlights
Alizarin and purpurin are di- and trihydroxyanthraquinones derived from Rubia tinctorum L
Qualitative determination of the extract The authentic standards alizarin and purpurin as well as the purified aqueous extract of Rubia tinctorum L. were analyzed by LC–MS/MS method (Fig. 2)
In summary, we showed that the purpurin, a trihydroxyanthraquinone and an aqueous extract from transformed root culture of Rubia tinctorum L. had tumor growth inhibitory activity in melanoma cell lines with different metastatic ability, and their effects proved to be irreversible and unrelated to apoptosis induction
Summary
Alizarin and purpurin are di- and trihydroxyanthraquinones derived from Rubia tinctorum L. The effects of alizarin, purpurin and an aqueous extract from transformed hairy root culture of Rubia tinctorum L. were examined on (1) cell proliferation, (2) apoptosis, (3) cell adhesion/morphology and (4) migration (chemotaxis, chemokinesis) of human melanoma cell lines (A2058, HT168-M1) and human fibroblast cells (MRC-5), as well as (5) the aqueous extract was analytically characterized. Common madder (Rubia tinctorum L.) is a well-known, traditional medicinal plant. It contains substantial amount of anthraquinones in its root and rhizome. The pharmacologically important main components of Rubia tinctorum L. are di- and trihydroxyanthraquinones: alizarin (Fig. 1a), purpurin (Fig. 1b) and their derivatives, ruberythric acid (alizarin-primeveroside), pseudopurpurin and lucidin-primeveroside [3]. Several other anthraquinones were identified as munjistin, pseudopurpurin, nordamnacanthal and lucidin [5, 6]
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