Cytotoxicity of 35 medicinal plants from Sudan towards sensitive and multidrug-resistant cancer cells

Mohamed E M Saeed, Haider Abdelgadir, Yoshikazu Sugimoto, Hassan E. Khalid, Thomas Efferth

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background Cancer is a complex disease with multiple genetic and epigenetic alterations. Since decades, the hallmark of cancer therapy is chemotherapy. Cytotoxic drugs erase rapidly dividing cells without sufficient differentiation between normal and cancerous cells resulting in severe side effects in normal tissues. Recently, strategies for cancer treatment focused on targeting specific proteins involved in tumor growth and progression. The present study was designed to investigate the cytotoxicity of 65 crude extracts from 35 Sudanese medicinal plants towards various cancer cell lines expressing molecular mechanisms of resistance towards classical chemotherapeutics (two ATP-binding cassette transporters, ABCB1 (P-glycoprotein) and ABCB5, tumor suppressor p53, epidermal growth factors receptor (EGFR). And the aim was to identify plant extracts and isolated compounds thereof with activity towards otherwise drug-resistant tumor cells. Methods Cold maceration was performed to obtain crude extracts from the plants. The resazurin assay was used to determine cytotoxicity of the plant extracts. Microarray-based mRNA expression profiling, COMPARE, and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to ambrosin, the main constituent of the most active extract Ambrosia maritima. Results The results of the resazurin assay on different tumors showed that Lawsonia inermis, Trigonella foenum-graecum and Ambrosia maritma were the most active crude extracts. Ambrosin was selected as one active principle of A. maritima for microarray-based expression profiling. Genes from various functional groups (transcriptional regulators, signal transduction, membrane transporters, cytoskeleton organization, chaperones, immune system development and DNA repair) were significantly correlated with response of tumor cell lines to ambrosin. Conclusion The results revealed cytotoxicity and pharmacogenomics studies of Sudanese medicinal plants provide an attractive strategy for the development of novel cancer therapeutics with activity towards cell lines that resistance to established anticancer agents.

Original languageEnglish
Pages (from-to)644-658
Number of pages15
JournalJournal of Ethnopharmacology
Volume174
DOIs
Publication statusPublished - 2015 Apr 1

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Sudan
Medicinal Plants
Neoplasms
Complex Mixtures
Ambrosia
Plant Extracts
Lawsonia Plant
Trigonella
Cell Line
ATP-Binding Cassette Transporters
Membrane Transport Proteins
P-Glycoprotein
Protein Transport
Tumor Cell Line
Cytoskeleton
Epidermal Growth Factor Receptor
Epigenomics
DNA Repair
Pharmaceutical Preparations
Antineoplastic Agents

Keywords

  • Chemotherapy
  • Cytotoxicity
  • Microarray analysis
  • Multidrug resistance
  • Sudanese medicinal plants Phytotherapy

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Cytotoxicity of 35 medicinal plants from Sudan towards sensitive and multidrug-resistant cancer cells. / Saeed, Mohamed E M; Abdelgadir, Haider; Sugimoto, Yoshikazu; Khalid, Hassan E.; Efferth, Thomas.

In: Journal of Ethnopharmacology, Vol. 174, 01.04.2015, p. 644-658.

Research output: Contribution to journalArticle

Saeed, Mohamed E M ; Abdelgadir, Haider ; Sugimoto, Yoshikazu ; Khalid, Hassan E. ; Efferth, Thomas. / Cytotoxicity of 35 medicinal plants from Sudan towards sensitive and multidrug-resistant cancer cells. In: Journal of Ethnopharmacology. 2015 ; Vol. 174. pp. 644-658.
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AU - Efferth, Thomas

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N2 - Background Cancer is a complex disease with multiple genetic and epigenetic alterations. Since decades, the hallmark of cancer therapy is chemotherapy. Cytotoxic drugs erase rapidly dividing cells without sufficient differentiation between normal and cancerous cells resulting in severe side effects in normal tissues. Recently, strategies for cancer treatment focused on targeting specific proteins involved in tumor growth and progression. The present study was designed to investigate the cytotoxicity of 65 crude extracts from 35 Sudanese medicinal plants towards various cancer cell lines expressing molecular mechanisms of resistance towards classical chemotherapeutics (two ATP-binding cassette transporters, ABCB1 (P-glycoprotein) and ABCB5, tumor suppressor p53, epidermal growth factors receptor (EGFR). And the aim was to identify plant extracts and isolated compounds thereof with activity towards otherwise drug-resistant tumor cells. Methods Cold maceration was performed to obtain crude extracts from the plants. The resazurin assay was used to determine cytotoxicity of the plant extracts. Microarray-based mRNA expression profiling, COMPARE, and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to ambrosin, the main constituent of the most active extract Ambrosia maritima. Results The results of the resazurin assay on different tumors showed that Lawsonia inermis, Trigonella foenum-graecum and Ambrosia maritma were the most active crude extracts. Ambrosin was selected as one active principle of A. maritima for microarray-based expression profiling. Genes from various functional groups (transcriptional regulators, signal transduction, membrane transporters, cytoskeleton organization, chaperones, immune system development and DNA repair) were significantly correlated with response of tumor cell lines to ambrosin. Conclusion The results revealed cytotoxicity and pharmacogenomics studies of Sudanese medicinal plants provide an attractive strategy for the development of novel cancer therapeutics with activity towards cell lines that resistance to established anticancer agents.

AB - Background Cancer is a complex disease with multiple genetic and epigenetic alterations. Since decades, the hallmark of cancer therapy is chemotherapy. Cytotoxic drugs erase rapidly dividing cells without sufficient differentiation between normal and cancerous cells resulting in severe side effects in normal tissues. Recently, strategies for cancer treatment focused on targeting specific proteins involved in tumor growth and progression. The present study was designed to investigate the cytotoxicity of 65 crude extracts from 35 Sudanese medicinal plants towards various cancer cell lines expressing molecular mechanisms of resistance towards classical chemotherapeutics (two ATP-binding cassette transporters, ABCB1 (P-glycoprotein) and ABCB5, tumor suppressor p53, epidermal growth factors receptor (EGFR). And the aim was to identify plant extracts and isolated compounds thereof with activity towards otherwise drug-resistant tumor cells. Methods Cold maceration was performed to obtain crude extracts from the plants. The resazurin assay was used to determine cytotoxicity of the plant extracts. Microarray-based mRNA expression profiling, COMPARE, and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to ambrosin, the main constituent of the most active extract Ambrosia maritima. Results The results of the resazurin assay on different tumors showed that Lawsonia inermis, Trigonella foenum-graecum and Ambrosia maritma were the most active crude extracts. Ambrosin was selected as one active principle of A. maritima for microarray-based expression profiling. Genes from various functional groups (transcriptional regulators, signal transduction, membrane transporters, cytoskeleton organization, chaperones, immune system development and DNA repair) were significantly correlated with response of tumor cell lines to ambrosin. Conclusion The results revealed cytotoxicity and pharmacogenomics studies of Sudanese medicinal plants provide an attractive strategy for the development of novel cancer therapeutics with activity towards cell lines that resistance to established anticancer agents.

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