Histone deacetylase (HDAC) inhibitory and antiproliferative activities of phenolic-rich extracts derived from the rhizome of Hydnophytum formicarum Jack.: sinapinic acid acts as HDAC inhibitor

BMC Complementary and Alternative Medicine

Banchob Sripa²  Arpa Surapaitoon²  Chanokbhorn Phaosiri¹  Prasan Sawatsitang³  Suporn Nuchadomrong³  Somprasong Khaopha³  Suwatchai Misuna³  Thanaset Senawong³ 

[1] Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand;Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand

关键词: Sinapinic acid;    Anticancer activity;    HDAC inhibitors;    Hydnophytum formicarum Jack;   

Others  :  1220988
DOI  :  10.1186/1472-6882-13-232

 received in 2013-03-02, accepted in 2013-09-17,  发布年份 2013

【 摘 要 】

Background

The rhizome of Hydnophytum formicarum Jack., a medicinal plant known in Thai as Hua-Roi-Roo, has been used in Thai traditional herbal medicine for treatment of cancer. We assessed the ability of its ethanolic and phenolic-rich extracts and its major phenolic compound, sinapinic acid, possessing histone deacetylase (HDAC) inhibitory activity to inhibit proliferation of 5 human cancer cell lines.

Methods

HeLa cells were used to study HDAC inhibitory activity of the extracts, sinapinic acid, and a well-known HDAC inhibitor sodium butyrate. Five human cancer cell lines and one non-cancer cell line were used to study antiproliferative activities of the plant extracts, sinapinic acid and sodium butyrate, comparatively.

Results

Results indicated that ethanolic and phenolic-rich extracts of H. formicarum Jack. rhizome possessed both antiproliferative activity and HDAC inhibitory activity in HeLa cells. Sinapinic acid, despite its lower HDAC inhibitory activity than the well-known HDAC inhibitor sodium butyrate, inhibited the growth of HeLa and HT29 cells more effectively than sodium butyrate. However, sinapinic acid inhibited the growth of HCT116 and Jurkat cells less effectively than sodium butyrate. The non-cancer cell line (Vero cells) and breast cancer cell line (MCF-7 cells) appeared to be resistant to both sinapinic acid and sodium butyrate. The growth inhibitory effects of the ethanolic and phenolic-rich extracts and sinapinic acid in HeLa cells were mediated by induction of apoptosis.

Conclusions

The results of this study support the efficacy of H. formicarum Jack. rhizome ethanolic and phenolic-rich extracts for the treatment of cervical cancer, colon cancer, and T- cell leukemia in an alternative medicine. Further studies of other active ingredients from this plant are needed.

【 授权许可】

   
2013 Senawong et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Arokhayasarn KT: Cancer treatment by Thai Herbal Nursing Home; Arokhayasarn [online]. 2013. Available: http://www.khampramong.org/aro3.html webcite [accessed 2 September 2013]
• [2]Itharat A, Supavita T, Jusanit P, Singchangchai P, Subchareon P, Deevisad G, Ubonkaw P, Ratanasuwan P, Kajpunyapong V, Muangsrinun R: Survey of Medicinal Plants and Local Folk Wisdom in Southern Thailand: Case Study at Talebun National Parks. Songkla: Prince of Songkla University; 1999:82-115.
• [3]Itharat A, Singchangchai P, Subchareon P, Supavita T, Ubonkaw P, Ratanasuwan P, Kummee S, Srisuchatum P: Folk Wisdom About Treatment of Traditional Doctors in Southern Thailand. Songkla: Prince of Songkla University: Focus Groups Discussion; 2002:83.
• [4]Manosroi V, Boonpisuttinant K, Manosroi W, Manosroi A: Anti-proliferative activities on HeLa cancer cell line of Thai medicinal plant recipes selected from MANOSROI II database. J Ethnopharmacol 2012, 142:422-431.
• [5]Ueda JY, Tezuka Y, Banskota AH, Le Tran Q, Tran QK, Harimaya Y, Saiki I, Kadota S: Antiproliferative activity of Vietnamese medicinal plants. Biol Pharm Bull 2002, 25:753-760.
• [6]Itharat A, Houghton PJ, Eno-Amooquaye E, Burke PJ, Sampson JH, Raman A: In vitro cytotoxic activity of Thai medicinal plants used traditionally to treat cancer. J Ethnopharmacol 2004, 90:33-38.
• [7]Prachayasittikul S, Buraparuangsang P, Worachartcheewan A, Isarankura-Na-Ayudhya C, Ruchirawat S, Prachayasittikul V: Antimicrobial and antioxidative activities of bioactive constituents from Hydnophytum formicarum Jack. Molecules 2008, 13:904-921.
• [8]Senawong T, Pongthaisong S, Chungjatupornchai W, Nuchadomrong S, Swatsitang P: Proceedings of the 31st Congress on Science and Technology of Thailand, Technopolis, Suranaree Universtity of Technology. Proceedings of the 31st Congress on Science and Technology of Thailand, Technopolis, Suranaree Universtity of Technology: Nakhon Ratchasima, Thailand; 2005.
• [9]Marks PA, Xu WS: Histone Deacetylase Inhibitors: Potential in Cancer Therapy. J Cell Biochem 2009, 107:600-608.
• [10]Martinez-Iglesias O, Ruiz-Llorente L, Sanchez-Martinez R, Garcia L, Zambrano A, Aranda A: Histone deacetylase inhibitors: mechanism of action and therapeutic use in cancer. Clin Transl Oncol 2008, 10:395-398.
• [11]Rasheed WK, Johnstone RW, Prince HM: Histone deacetylase inhibitors in cancer therapy. Expert Opin Investig Drugs 2007, 16:659-678.
• [12]Riester D, Hildmann C, Schwienhorst A: Histone deacetylase inhibitors–turning epigenic mechanisms of gene regulation into tools of therapeutic intervention in malignant and other diseases. Appl Microbiol Biotechnol 2007, 75:499-514.
• [13]Wu D, Huang Q, Zhang Y, Zhang Q, Liu Q, Gao J, Cao Z, Zhu R: Screening of selective histone deacetylase inhibitors by proteochemometric modeling. BMC Bioinforma 2012, 13:212. doi:10.1186/1471-2105-13-212 BioMed Central Full Text
• [14]Bots M, Johnstone RW: Rational Combinations Using HDAC Inhibitors. Clin Cancer Res 2009, 15:3970-3977.
• [15]Carew JS, Giles FJ, Nawrocki ST: Histone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapy. Cancer Lett 2008, 269:7-17.
• [16]Bora-Tatar G, Dayangac-Erden D, Demir AS, Dalkara S, Yelekci K, Erdem-Yurter H: Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies. Bioorg Med Chem 2009, 17:5219-5228.
• [17]Jiao J, Fang H, Wang X, Guan P, Yuan Y, Xu W: Design, synthesis and preliminary biological evaluation of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives as novel histone deacetylase inhibitors. Eur J Med Chem 2009, 44:4470-4476.
• [18]Hsu CL, Lo WH, Yen GC: Gallic acid induces apoptosis in 3T3-L1 pre-adipocytes via a fas- and mitochondrial-mediated pathway. J Agr Food Chem 2007, 55:7359-7365.
• [19]Dayangac-Erden D, Bora G, Ayhan P, Kocaefe C, Dalkara S, Yelekci K, Demir AS, Erdem-Yurter H: Histone Deacetylase Inhibition Activity and Molecular Docking of (E)-Resveratrol: Its Therapeutic Potential in Spinal Muscular Atrophy. Chem Biol Drug Des 2009, 73:355-364.
• [20]Krygier K, Sosulski F, Hogge L: Free, esterified and insoluble-bound phenolic acids. 1. Extraction and purification procedure. J Agr Food Chem 1982, 30:330-334.
• [21]Torres AM, Mau-Lastovicka T, Rezaaiyan R: Total phenolics and high-performance liquid chromatography of phenolic acids of avocado. J Agr Food Chem 1987, 35:921-925.
• [22]Smith JS, Brachmann CB, Celic I, Kenna MA, Muhammad S, Starai VJ, Avalos JL, Escalante-Semerena JC, Grubmeyer C, Wolberger C, Boeke JD: A phylogenetically conserved NAD + −dependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci U S A 2000, 97:6658-6663.
• [23]Lindemann RK, Gabrielli B, Johnstone RW: Histone-deacetylase inhibitors for the treatment of cancer. Cell Cycle 2004, 3:779-788.
• [24]Bolden JE, Peart MJ, Johnstone RW: Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006, 5:769-784.
• [25]Lin HY, Chen CS, Lin SP, Weng JR, Chen CS: Targeting histone deacetylase in cancer therapy. Med Res Rev 2006, 26:397-413.
• [26]Waldecker M, Kautenburger T, Daumann H, Busch C, Schrenk D: Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. J Nutr Biochem 2008, 19:587-593.
• [27]De Ruijter AJM, Van Gennip AH, Caron HN, Kemp S, Van Kuilenburg ABP: Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003, 370:737-749.
• [28]Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian XZ, Mills E, Berghs SC, Carey N, Finn PW, Collins LS, Tumber A, Ritchie JW, Jensen PB, Lichenstein HS, Sehested M: Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J 2008, 409:581-589.
• [29]Gawlik-Dziki U, Świeca M, Dziki D: Comparison of Phenolic Acids Profile and Antioxidant Potential of Six Varieties of Spelt (Triticum spelta L.). J Agric Food Chem 2012, 60:4603-4612.
• [30]Kretzner L, Scuto A, Dino PM, Kowolik CM, Wu J, Ventura P, Jove R, Forman SJ, Yen Y, Kirschbaum MH: Combining histone deacetylase inhibitor vorinostat with aurora kinase inhibitors enhances lymphoma cell killing with repression of c-Myc, hTERT, and micro-RNA levels. Cancer Res 2011, 71:3912-3920.
• [31]Cheriyath V, Kuhns MA, Kalaycio ME, Borden EC: Potentiation of apoptosis by histone deacetylase inhibitors and doxorubicin combination: cytoplasmic cathepsin B as a mediator of apoptosis in multiple myeloma. Br J Cancer 2011, 104:957-967.