Targeted tumor therapy by Rubia tinctorum L.

Analytical characterization of hydroxyanthraquinones and investigation of their selective cytotoxic, adhesion and migration modulator effects on melanoma cell lines (A2058 and HT168-M1)

Eszter Lajkó, Péter Bányai, Zsófia Zámbó, László Kursinszki, E. Szőke, L. Kőhidai

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6 Citations (Scopus)

Abstract

Background: Alizarin 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. Methods: The 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. Results: In 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. Conclusions: Our 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.

Original languageEnglish
Article number119
JournalCancer Cell International
Volume15
Issue number1
DOIs
Publication statusPublished - Dec 18 2015

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Rubia
Melanoma
Anthraquinones
Cell Line
Neoplasms
Fibroblasts
Chemotaxis
Cell Adhesion
Microscopy
Therapeutics
Apoptosis
Drug Delivery Systems
Electric Impedance
Pharmaceutical Preparations
Antineoplastic Agents
Analysis of Variance
Flow Cytometry
High Pressure Liquid Chromatography
Cell Proliferation
purpurin

Keywords

  • Cell adhesion
  • Holographic microscope
  • HPLC-MS/MS
  • Hydroxyanthraquinone
  • Impedimetry
  • Melanoma
  • Migration
  • Purpurin
  • Rubia tinctorum L.
  • Targeted therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Genetics

Cite this

@article{6c62cff2cc684423be5d4cf1507a454c,
title = "Targeted tumor therapy by Rubia tinctorum L.: Analytical characterization of hydroxyanthraquinones and investigation of their selective cytotoxic, adhesion and migration modulator effects on melanoma cell lines (A2058 and HT168-M1)",
abstract = "Background: Alizarin 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. Methods: The 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{\circledR} 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. Results: In 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. Conclusions: Our 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.",
keywords = "Cell adhesion, Holographic microscope, HPLC-MS/MS, Hydroxyanthraquinone, Impedimetry, Melanoma, Migration, Purpurin, Rubia tinctorum L., Targeted therapy",
author = "Eszter Lajk{\'o} and P{\'e}ter B{\'a}nyai and Zs{\'o}fia Z{\'a}mb{\'o} and L{\'a}szl{\'o} Kursinszki and E. Szőke and L. Kőhidai",
year = "2015",
month = "12",
day = "18",
doi = "10.1186/s12935-015-0271-4",
language = "English",
volume = "15",
journal = "Cancer Cell International",
issn = "1475-2867",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Targeted tumor therapy by Rubia tinctorum L.

T2 - Analytical characterization of hydroxyanthraquinones and investigation of their selective cytotoxic, adhesion and migration modulator effects on melanoma cell lines (A2058 and HT168-M1)

AU - Lajkó, Eszter

AU - Bányai, Péter

AU - Zámbó, Zsófia

AU - Kursinszki, László

AU - Szőke, E.

AU - Kőhidai, L.

PY - 2015/12/18

Y1 - 2015/12/18

N2 - Background: Alizarin 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. Methods: The 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. Results: In 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. Conclusions: Our 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.

AB - Background: Alizarin 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. Methods: The 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. Results: In 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. Conclusions: Our 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.

KW - Cell adhesion

KW - Holographic microscope

KW - HPLC-MS/MS

KW - Hydroxyanthraquinone

KW - Impedimetry

KW - Melanoma

KW - Migration

KW - Purpurin

KW - Rubia tinctorum L.

KW - Targeted therapy

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U2 - 10.1186/s12935-015-0271-4

DO - 10.1186/s12935-015-0271-4

M3 - Article

VL - 15

JO - Cancer Cell International

JF - Cancer Cell International

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