title: Cytotoxicity of 35 medicinal plants from Sudan towards sensitive and multidrug-resistant cancer cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Mohamed E M
authors.initials: ME
authors.lastname: Saeed
authors.affiliation: Department of Pharmacognosy, University of Khartoum, Khartoum, Sudan.
authors.forename: Haider
authors.initials: H
authors.lastname: Abdelgadir
authors.affiliation: Division of Chemotherapy, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Department of Pharmacognosy, University of Khartoum, Khartoum, Sudan.
authors.forename: Hassan E
authors.initials: HE
authors.lastname: Khalid
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany. Electronic address: efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007202:Indicators and Reagents; D010078:Oxazines; D010597:Pharmacogenetics; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane; D013397:Sudan; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014966:Xanthenes
chemical_list: C513055:ABCB1 protein, human; C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D010078:Oxazines; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D016159:Tumor Suppressor Protein p53; D014966:Xanthenes; C005843:resazurin; C010675:ambrosin
keywords: Chemotherapy; Cytotoxicity; Microarray analysis; Multidrug resistance; Phytotherapy; Sudanese medicinal plants