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3D cytotoxic and histon deacetylase (HDAC) inhibitory activities of triterpenoids isolated from leaves of Viburnum sambucinum

Nguyen Thanh Tra, Nguyen Thi Thu Ha, Ba Thi Cham, Le Thi Tu Anh, Do Thi Thao, Nguyen Thi Nga, Doan Thi Mai Huong, Pham Van Cuong


The plant Viburnum sambucinum has been known under the local name “Vót dạng cơm cháy” belongs to Viburnum genus, a member of the Caprifoliaceae family. Many plants of Viburnum genus are well known for their medicinal properties and are used in the folk medicine for the treatment of various diseases. A variety of structures have been reported from the plants of the genus, such as diterpenes, triterpenes, iridoids, sesquiterpenes, flavonoids, etc. In this study, we describe 3D cytotoxic and histone deacetylase (HDAC) inhibitory activities of two nordammarane triterpenoids hupehenol D (1) and 12β-hydoxy-3,15-dioxo-20,21,22-23,24,25,26,27-octanordammanrane (2) isolated from the leaves of Viburnum sambucinum. The result showed that (1) and (2) exhibited a strong activity against 3D models of LLC cell line with the IC50 value ​​of 25.89 µM and 15.58 µM, respectively. Compound 1 weakly inhibited activity of enzyme HDAC with the IC50 of 20.78±2.86 mM while compound 2 exhibited no effect on HDAC at 25 mM.

Keywords. Viburnum sambucinum, Caprifoliaceae, hupehenol D (1), 12β-hydoxy-3,15-dioxo-20,21,22-23,24,25,26,27-octanordammanrane (2), 3D cytotoxic, HDAC inhibitory activity.


Viburnum sambucinum, Caprifoliaceae, hupehenol D (1), 12β-hydoxy-3,15-dioxo-20,21,22-23,24,25,26,27-octanordammanrane (2), 3D cytotoxic, HDAC inhibitory activity

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World Health Organization. Cancer Fact Sheet. February 2011. Available online: mediacentre/factsheets/fs297/en/index.html (accessed on 30 March 2012).

Abhishek Bhanot, Rohini Sharma, Malleshappa N. Noolvi. Natural sources as potential anti-cancer agents: A review, International Journal of Phytomedicine, 3, 09-26 (2011).

Cragg GM, Kingston DGI, Newman DJ. Anticancer Agents from Natural Products. Taylor & Francis Group, Boca Raton, FL. Brunner-Routledge Psychology Press (2005).

Lobstein A., Haan-Archipoff G., Englert J., Kuhry J. G., Anton R. Chemotaxonomical investigation in the genus Viburnum, Phytochemistry, 50, 1175-1180 (1999).

Wang X. Y., Shi H. M., Li X. B. Chemical constituents of plants from the genus Viburnum, Chemistry and Biodiversity, 7(3), 567-593 (2010).

Xiaohua Wang and Wei Wang. Cytotoxic and Radical Scavenging Nor-Dammarane Triterpenoids from Viburnum mongolicum, Molecules, 18, 1405-1417 (2013).

M. Kubo, Y. Kishimoto, K. Harada, H. Hioki, and Y. Fukuyama. NGF-potentiating vibsane-type diterpenoids from Viburnum sieboldii, Bioorg. Med. Chem. Lett., 20(8), 2566-71 (2010).

Nguyen Thanh Tra, Truong Bich Ngan, Doan Thi Mai Huong, Do Thi Thao, Marc Litaudon, Nguyen Van Hung, Chau Van Minh, Pham Van Cuong. Chemical constituents and cytotoxic activities of Viburnum sambucinum leaves (Caprifoliaceae), Vietnam Journal

of Chemistry, 54(5), 614-619 (2016).

Kunz-Schughart LA., Freyer JP., Hofstaedter F., Ebner R. The use of 3-D cultures for high-throughput screening: the multicellular spheroid model, J. Biomol. Screen, 9(4), 273-285 (2004).

Vinci M., Gowan S., Boxall F., Patterson L., Zimmermann M., Court W., Lomas C., Mendiola M., Hardisson D., Eccles SA. Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation, BMC Biol., 10, 29 (2012).

Balis FM. et al. Evolution of Anticancer Drug Discovery and the Role of Cell-Based Screening, Journal of the National Cancer Institute, 94(2), 78-79 (2002).

Zang R., Li D., Tang IC., Wang J., Yang ST. Cell-Based Assays in High-Throughput Screening for Drug Discovery, International Journal of Biotechnology for Wellness Industries, 1, 31-51 (2012).

Basu S., Yang ST. Astrocyte growth and glial cell line-derived neurotrophic factor secretion in three-dimensional polyethylene terephthalate fibrous matrices, Tissue Eng., 11, 940-52 (2005).

Edmondson R., Broglie JJ., Adcock AF., Yang L. Three-dimensional cell culture systems and their applications in drugs discovery and cell-based biosensors, Assay Drug Dev Technol., 12(4), 207-218 (2014)

Zietarska M., Maugard CM., Filali-Mouhim A. et al. Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC), Mol. Carcinog., 46, 872-885 (2007).

Lee J., Cuddihy MJ., Kotov NA. Three-dimensional cell culture matrices: state of the art, Tissue Eng Part B Rev., 14, 61-86 (2008).

Loessner D., Stok KS., Lutolf MP., Hutmacher DW., Clements JA., Rizzi SC. Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells, Biomaterials, 31, 8494-8506 (2010).

Karlsson H., Fryknäs M., Larsson R., Nygren P. Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system, Exper. Cell. Res., 318, 1577-1585 (2012).

Adcock AF., Trivedi G., Edmondson R., Spearman C. and Yang L. Three-Dimensional (3D) Cell Cultures in Cell-based Assays for in-vitro, J. Anal. Bioanal. Tech., 6(3), 2-12 (2015).

Mottamal M., Zheng S., Huang TL., Wang G. Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents, Molecules, 20(3), 3898-3941 (2015).


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