L-01: ELUCIDATING POLYPHARMACOLOGICAL MECHANISMS OF CANCER CHEMOPREVENTION BY MANGIFERIN AND WITHAFERIN

J Pharm Pharmacogn Res 3(suppl. 1): S1, 2015

Proceedings of the 4th International Symposium on Pharmacology of Natural Products FAPRONATURA 2015  September 21st-25th, 2015; Cuban Society of Pharmacology. Topes de Collantes, Sancti Spiritus, Cuba.

Lecture

L-01: ELUCIDATING POLYPHARMACOLOGICAL MECHANISMS OF CANCER CHEMOPREVENTION BY MANGIFERIN AND WITHAFERIN A BY TRANSCRIPTOME AND (CHEMO) PROTEOME BASED PATHWAY AND DRUG TARGET ENRICHMENT ANALYSIS

Hernández-Balmaseda I1, Szarc vel Szic K2, Chirumamilla CS2, Palagani A2, Hassania B3,4, Declerck K2, Dom M2, Naulaerts S5, Op de Beeck K6, Kaileh M4,7, Haegeman G4, Van Camp G6, Laukens K5, Heyninck K4, Van Ostade X2, Vanden Berghe T3, Vandenabeele P3, Rodeiro-Guerra I1, Delgado-Hernández R8, Vanden Berghe W2,4.

1Laboratory of Pharmacology, Bioactive Marine Center, Havana, Cuba.
2Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp (UA), Antwerp, Belgium.
3 Inflammation Research Center, VIB, Ghent University, Belgium.
4Laboratory of GPCR Expression & Signal Transduction (L-GEST), Ghent University, Belgium.
5Advanced Database Research and Modeling (ADReM), Biomina, University of Antwerp (UA), Belgium.
6Laboratory of Cancer Research and Clinical Oncology, Center of Medical Genetics, University of Antwerp, Belgium.
7Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, USA.
8Division of Research and Development, Center for Pharmaceutical Research and Drug Development (CIDEM), Havana, Cuba.

Drugs designed to act against individual molecular targets usually cannot combat multigenic diseases such as cancer, or diseases that affect multiple tissues or cell types such as diabetes and immunoinflammatory disorders. Combination drugs that affect multiple targets simultaneously are better at controlling complex disease systems, are less prone to drug resistance and are the standard of care in many important therapeutic areas.  The identification of biologically active and potentially therapeutically useful pharmacophores from natural products has been a long-term focus in the pharmaceutical industry. The steroidal withanolide withaferin A (Withania somnifera) and the xanthone polyphenol mangiferin (Mangifera indica) hold much promise as potential novel cancer chemopreventive or therapeutic compounds. However, it is a great challenge to elucidate their polypharmacological anti-cancer mechanisms. To address this challenge, we apply bioinformatics methods to identify multiple targets of chemical agents through analysis of the gene expression profiles following in vitro/in vivo treatment. By using transcriptome based pathway and drug target enrichment analysis and pharmapper in silico modeling studies, it is possible to identify activated or repressed pathways and to predict possible molecular targets. Direct phytochemical-protein interactions can be verified by (chemo)proteomic approaches. The results show that the medicinal effects of withaferin A and mangiferin extend far beyond well-known antioxidant activities of natural products. This method is also applicable to dissect the polypharmacology of other natural products or crude plant extracts.

Citation Format: Hernández-Balmaseda I, Szarc vel Szic K, Chirumamilla CS, Palagani A, Hassania B, Declerck K, Dom M, Naulaerts S, Op de Beeck K, Kaileh M, Haegeman G, Van Camp G, Laukens K, Heyninck K, Van Ostade X, Vanden Berghe T, Vandenabeele P, Rodeiro-Guerra I, Delgado-Hernández R, Vanden Berghe W (2015) Elucidating polypharmacological mechanisms of cancer chemoprevention by mangiferin and withaferin a by transcriptome and (chemo) proteome based pathway and drug target enrichment analysis. Hepatotoxicity and oxidative stress biomarker study of peg-coated and non-coated gold nanoparticles in Sprague-Dawley rats. [Abstract]. In: Proceedings of the FAPRONATURA 2015; 2015 Sep 21-25; Topes de Collantes, Sancti Spiritus: CSF. J Pharm Pharmacogn Res 3(Suppl. 1): S1 . Abstract nr L-01.