Cytotoxic Activity and G1 Cell Cycle Arrest of a Dienynone from Echinacea pallida

Abstract

In the present study, a further investigation of the cytotoxic activity of an acetylenic constituent of Echinacea pallida roots, namely, pentadeca-(8Z,13Z)-dien-11-yn-2-one, was performed, revealing a concentration-dependent cytotoxicity on several human cancer cell lines, including leukemia (Jurkat and HL-60), breast carcinoma (MCF-7), and melanoma (MeWo) cells. As part of its mechanism of action, the ability of this constituent to arrest the cell cycle in the G1 phase was demonstrated on HL-60 cells. Furthermore, a stability test of the target compound over 72 h was carried out, indicating that the cytotoxic activity can be attributed mainly to the genuine, not oxidized, molecule.

Key words

Echinacea pallida (Asteraceae) - acetylenes - polyenes - cell cycle - cytotoxicity - cancer

References

• 1 Gertsch J. Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system.  Planta Med. 2008;  74 638-650
• 2 Woelkart K, Linde K, Bauer R. Echinacea for preventing and treating the common cold.  Planta Med. 2008;  74 633-637
• 3 Richardson M A, Sanders T, Palmer J L, Greisinger A, Singletary S E. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology.  J Clin Oncol. 2000;  18 2505-2514
• 4 Dy G K, Bekele L, Hanson L J, Furth A, Mandrekar S, Sloan J A, Adjei A A. Complementary and alternative medicine use by patients enrolled onto phase I clinical trials.  J Clin Oncol. 2004;  22 4810-4815
• 5 Chicca A, Adinolfi B, Martinotti E, Fogli S, Breschi M C, Pellati F, Benvenuti S, Nieri P. Cytotoxic effects of Echinacea root hexanic extracts on human cancer cell lines.  J Ethnopharmacol. 2007;  110 148-153
• 6 Pellati F, Calò S, Benvenuti S, Adinolfi B, Nieri P, Melegari M. Isolation and structure elucidation of cytotoxic polyacetylenes and polyenes from Echinacea pallida.  Phytochemistry. 2006;  67 1359-1364
• 7 Pellati F, Calò S, Benvenuti S. High-performance liquid chromatography analysis of polyacetylenes and polyenes in Echinacea pallida by using a monolithic reversed-phase silica column.  J Chromatogr A. 2007;  1149 56-65
• 8 Morandi S, Pellati F, Ori C, Adinolfi B, Nieri P, Benvenuti S, Prati F. Isolation, structure elucidation and total synthesis of a cytotoxic dienyone from Echinacea pallida.  Org Biomol Chem. 2008;  6 4333-4339
• 9 Barnes J, Anderson L A, Gibbons S, Phillipson J D. Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt., Echinacea purpurea (L.) Moench): a review of their chemistry, pharmacology and clinical properties.  J Pharm Pharmacol. 2005;  57 929-954
• 10 Chicca A, Pellati F, Adinolfi B, Matthias A, Massarelli I, Benvenuti S, Martinotti E, Bianucci A M, Bone K, Lehmann R, Nieri P. Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida.  Br J Pharmacol. 2008;  153 879-885
• 11 Romiti N, Pellati F, Nieri P, Benvenuti S, Adinolfi B, Chieli E. P-Glycoprotein inhibitory activity of lipophilic constituents of Echinacea pallida roots in a human proximal tubular cell line.  Planta Med. 2008;  74 264-266
• 12 Tassone P, Tagliaferri P, Perricelli A, Blotta S, Quaresima B, Martelli M L, Goel A, Barbieri V, Costanzo F, Boland C R, Venuta S. BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells.  Br J Cancer. 2003;  88 1285-1291
• 13 Mariggiò M A, Cafaggi S, Ottone M, Parodi B, Vannozzi M O, Mandys V, Viale M. Inhibition of cell growth, induction of apoptosis and mechanism of action of the novel platinum compound cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate.  Invest New Drugs. 2004;  22 3-16
• 14 Bernart M W, Cardellina 2nd J H, Balaschak M S, Alexander M R, Shoemaker R H, Boyd M R. Cytotoxic falcarinol oxylipins from Dendropanax arboreus.  J Nat Prod. 1996;  59 748-753
• 15 Kuo Y C, Lin Y L, Huang C P, Shu J W, Tsai W J. A tumor cell growth inhibitor from Saposhnikovae divaricata.  Cancer Invest. 2002;  20 955-964
• 16 Moon J, Yu S J, Kim H S, Sohn J. Induction of G(1) cell cycle arrest and p 27(KIP1) increase by panaxydol isolated from Panax ginseng.  Biochem Pharmacol. 2000;  59 1109-1116
• 17 Park C, Kim G Y, Kim G D, Lee W H, Cheong J H, Kim N D, Bae S J, Jung J H, Choi Y H. Suppression of U937 human monocytic leukemia cell growth by dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., via induction of Cdk inhibitor p 16 and down-regulation of pRB phosphorylation.  Oncol Rep. 2006;  16 171-176
• 18 Morandi S, Pellati F, Benvenuti S, Prati F. Total synthesis of a dienynone from Echinacea pallida.  Tetrahedron. 2008;  64 6324-6328
• 19 Bauer R, Khan I A, Wagner H. TLC and HPLC analysis of Echinacea pallida and E. angustifolia roots.  Planta Med. 1988;  54 426-430
• 20 Lee S K, Heo Y H, Steele V E, Pezzuto J M. Induction of apoptosis by 1,4-phenylenebis(methylene) selenocyanate in cultured human colon cancer cells.  Anticancer Res. 2002;  22 97-102