Mohamed E M Saeed1, Haider Abdelgadir2, Yoshikazu Sugimoto3, Hassan E Khalid2, Thomas Efferth4. 1. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany. 2. Department of Pharmacognosy, University of Khartoum, Khartoum, Sudan. 3. Division of Chemotherapy, Faculty of Pharmacy, Keio University, Tokyo, Japan. 4. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany. Electronic address: efferth@uni-mainz.de.
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.
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.
Authors: María L González; D Mariano A Vera; Jerónimo Laiolo; Mariana B Joray; Mariana Maccioni; Sara M Palacios; Gabriela Molina; Priscila A Lanza; Samanta Gancedo; Vivian Rumjanek; María C Carpinella Journal: Front Pharmacol Date: 2017-04-25 Impact factor: 5.810
Authors: Mohamed Saeed; Stefan Jacob; Louis P Sandjo; Yoshikazu Sugimoto; Hassan E Khalid; Till Opatz; Eckhard Thines; Thomas Efferth Journal: Front Pharmacol Date: 2015-11-09 Impact factor: 5.810
Authors: Thomas Efferth; Mohamed E M Saeed; Elhaj Mirghani; Awadh Alim; Zahir Yassin; Elfatih Saeed; Hassan E Khalid; Salah Daak Journal: Oncotarget Date: 2017-07-25
Authors: María Laura González; Mariana Belén Joray; Jerónimo Laiolo; María Inés Crespo; Sara María Palacios; Gustavo Miguel Ruiz; María Cecilia Carpinella Journal: Evid Based Complement Alternat Med Date: 2018-05-10 Impact factor: 2.629