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DOI: 10.1055/s-0034-1383146
Antiproliferative Activity of Artemisia asiatica Extract and Its Constituents on Human Tumor Cell Lines
Publikationsverlauf
received 19. Mai 2014
revised 09. September 2014
accepted 15. September 2014
Publikationsdatum:
08. Oktober 2014 (online)
![](https://www.thieme-connect.de/media/plantamedica/201418/lookinside/thumbnails/10.1055-s-0034-1383146-1.jpg)
Abstract
The extract of Artemisia asiatica herb with antiproliferative activity against four human tumor cell lines (A2780, A431, HeLa, and MCF7) was analyzed by the MTT assay, and bioassay-directed fractionation was carried out in order to identify the compounds responsible for the cytotoxic activity. Guaianolide (1–4), seco-guianolide (5), germacranolide (6) and eudesmanolide sesquiterpenes (7), monoterpenes (8, 9), including the new compound artemisia alcohol glucoside (8), and flavonoids (10–16) were isolated as a result of a multistep chromatographic procedure (CC, CPC, PLC, and gel filtration). The compounds were identified by means of UV, MS, and NMR spectroscopy, including 1H-and 13C-NMR, 1H-1H COSY, NOESY, HSQC, and HMBC experiments. The isolated compounds 1–16 were evaluated for their tumor cell growth-inhibitory activities on a panel of four adherent cancer cell lines, and different types of secondary metabolites were found to be responsible for the cytotoxic effects of the extract. Especially cirsilineol (13), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (3), and iso-seco-tanapartholide 3-O-methyl ester (5) exerted marked cytotoxic effects against the investigated cell lines, while jaceosidin (12), 6-methoxytricin (15), artecanin (2), and 5,7,4′,5′-tetrahydroxy-6,3′-dimethoxyflavone (14) were moderately active. All the sesquiterpenes and monoterpenes are reported here for the first time from this species, and in the case of artecanin (2), 3α-chloro-4β,10α-dihydroxy-1β,2β-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (4), ridentin (6), and ridentin B (7), previously unreported NMR spectroscopic data were determined.
Key words
Artemisia asiatica - Asteraceae - antiproliferative activity - sesquiterpene lactones - monoterpenes - flavonoids-
References
- 1 Morrissey C, Gallis B, Solazzi JW, Kim BJ, Gulati R, Vakar-Lopez F, Goodlett DR, Vessella RL, Sasaki T. Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer cells. Anticancer Drugs 2010; 21: 423-432
- 2 Hartwell JL. Plants used against cancer. A survey (Review). Lloydia 1968; 31: 71-170
- 3 Baek YH, Lee KN, Jun DW, Yoon BC, Kim JM, Oh TY, Lee OY. Augmenting effect of DA-9601 on ghrelin in an acute gastric injury model. Gut Liver 2011; 5: 52-56
- 4 Seo HJ, Park KK, Han SS, Chung WY, Son MW, Kim WB, Surh YJ. Inhibitory effects of the standardized extract (DA-9601) of Artemisia asiatica Nakai on phorbol ester-induced ornithine decarboxylase activity, papilloma formation, cyclooxygenase-2 expression, inducible nitric oxide synthase expression and nuclear transcription factor kappa B activation in mouse skin. Int J Cancer 2002; 100: 456-462
- 5 Réthy B, Csupor-Löffler B, Zupkó I, Hajdú Z, Máthé I, Hohmann J, Rédei T, Falkay G. Antiproliferative activity of Hungarian Asteraceae species against human cancer cell lines. Part I. Phytother Res 2007; 21: 1200-1208
- 6 Huneck S, Zdero C, Bohlmann F. Seco-guaianolides and other constituents from Artemisia species. Phytochemistry 1986; 25: 883-889
- 7 Marco JA, Sanz-Cervera JF, Manglano E, Sancenon F, Rustaiyan A, Kardar M. Sesquiterpene lactones from iranian Artemisia species. Phytochemistry 1993; 34: 1561-1564
- 8 Trifunović S, Milosavljević S, Vajs V, Macura S, Todorović N. Stereochemistry and conformations of natural 1,2-epoxy-guaianolides based on 1D and 2D NMR data and semiempirical calculations. Magn Reson Chem 2008; 46: 427-431
- 9 Trifunović S, Vajs V, Juranić Z, Žižak Z, Tešević V, Macura S, Milosavljević S. Cytotoxic constituents of Achillea clavennae from Montenegro. Phytochemistry 2006; 67: 887-893
- 10 Trifunovic S, Aljančić I, Vajs V, Macura S, Milosavljević S. Sesquiterpene lactones and flavonoids of Achillea depressa . Biochem Syst Ecol 2005; 33: 317-322
- 11 Tan RX, Jia JZ, Jakupovic J, Bohlmann F, Huneck S. Sesquiterpene lactones from Artemisia rutifolia . Phytochemistry 1991; 30: 3033-3035
- 12 Irwin MA, Lee KH, Simson RF, Geisman TA. Sesquiterpene lactones of Artemisia. Ridentin. Phytochemistry 1969; 8: 2009-2012
- 13 Asaruddin MR, Honda G, Tsubouchi A, Shimada JN, Aoki T, Kiuchi F. Trypanocydal constituents from Michelia alba . Nat Med 2003; 57: 61-65
- 14 Hajdú Z, Martins A, Orbán-Gyapai O, Forgo P, Jedlinszki N, Máthé I, Hohmann J. Xanthine oxidase inhibitory activity and antioxidant properties of extract and flavonoids of Artemisia asiatica . Rec Nat Prod 2014; 8: 299-302
- 15 Kalemba D. Constituents of the essential oil of Artemisia asiatica Nakai. Flavour Frag J 1999; 14: 173-176
- 16 Kalemba D, Kusewicz D, Świąder K. Antimicrobial properties of the essential oil of Artemisia asiatica Nakai. Phytother Res 2002; 16: 288-291
- 17 Oh TY, Shin CY, Sohn YS, Kim DH, Ahn BO, Lee EB, Park CH. Therapeutic effect of DA-9601 on chronic reflux gastritis induced by sodium taurocholate in rats. World J Gastroenterol 2005; 11: 7430-7435
- 18 Park BB, Yoon JS, Kim ES, Choi J, Won YW, Choi JH, Lee YY. Inhibitory effects of eupatilin on tumor invasion of human gastric cancer MKN-1 cells. Tumor Biol 2013; 34: 875-885
- 19 Reddy AM, Lee JY, Seo JH, Kim BH, Chung EY, Ryu SY, Kim YS, Lee CK, Min KR, Kim Y. Artemisolide from Artemisia asiatica, nuclear factor-kappaB inhibitor suppressing prostaglandin E2 and nitric oxide production in macrophages. Arch Pharm Res 2006; 29: 591-597
- 20 Kim JH, Kim H, Jeon SB, Son K, Kim EH, Kang SK, Sung N, Kwon BM. New sesquiterpene-monoterpene lactone, artemisolide, isolated from Artemisia argyi . Tetrahedron Lett 2002; 43: 6205-6208
- 21 Irwin MA, Geismann TA. Ridentin B: an eudesmanolide from Artemisia tripartita ssp. rupicola . Phytochemistry 1973; 12: 871-873
- 22 Csupor-Löffler B, Hajdú Z, Zupkó I, Molnár J, Forgo P, Vasas A, Kele Z, Hohmann J. Antiproliferative constituents of the roots of Conyza canadensis . Planta Med 2011; 77: 1183-1188
- 23 Forgo P, Zupkó I, Molnár J, Vasas A, Dombi G, Hohmann J. Bioactivity-guided isolation of antiproliferative compounds from Centaurea jacea L. Fitoterapia 2012; 83: 921-925