Antitumor Activity of Flavones Isolated from Artemisia argyi

Abstract

The flavones 5,6-dihydroxy-7,3′,4′-trimethoxyflavone (1), 5,6,4′-trihydroxy-7,3′-dimethoxyflavone (2), 5-hydroxy-3′,4′,6,7-tetramethoxyflavone, 5,7,3′-trihydroxy-6,4′,5′-trimethoxyflavone, ladanein, and hispidulin were isolated from the methanolic extracts of the aerial parts of Artemisia argyi and structures of the compounds were elucidated on the basis of their spectral data. These flavones inhibited farnesyl protein transferase with IC₅₀ values of 25 - 200 μg/mL. Compound 2 inhibited proliferation of a couple of tumor cell lines and also inhibited neovascularization in a chick chorioallantoic membrane assay. Without loss of body weight of nude mice, compounds 1 and 2 inhibited growth of a colon tumor (SW620) by 44.6 % and 14.6 %, respectively.

Abbreviations

FPTase:farnesyl protein transferase

CAM:chick embryo chorioallantoic membrane

Key words

Artemisia argyi - Compositae - Flavones - Farnesyl protein transferase - Angiogenesis

References

• 1 Tan R X, Zheng W F, Tang H Q. Biologically active substances from the genus Artemisia .  Planta Medica. 1988;  64 295-302
• 2 Lee S H, Kim M J, Bok S H, Lee H, Kwon B M, Shin J H, Seo Y. Arteminolide, an inhibitor of farnesyl transferase from Artemisia sylvatica .  J Org Chem. 1998;  63 7111-3
• 3 Lee S H, Kang H M, Song H C, Lee H, Lee U C, Song K H, Kim S H, Kwon B M. Sesquiterpene lactones, inhibitors of farnesyl protein transferase, isolated from the flower of Artemisia sylvatica .  Tetrahedron. 2000;  56 4711-5
• 4 Oliff A. Farnesyltransferase inhibitors: targeting the molecular basis of cancer.  Biochim Biophys Acta. 1999;  1423 C19-30
• 5 Adjei A A, Erlichman C, Davis J N, Cutler D L, Sloan J A, Marks R S, Hanson L J, Svingen P A, Atherton P, Bishop W R, Kirschmeier P, Kaufmann S H. A phase I trial of the farnesyl transferase inhibitor SCH66336: Evidence for biological and clinical activity.  Cancer Res. 2000;  60 1871-7
• 6 Kwon B M, Cho Y K, Lee S H, Nam J Y, Bok S H, Chun S K, Kim J A, Lee I R. 2′-Hydroxycinnamaldehyde from stem bark of Cinnamomum cassia .  Planta Medica. 1996;  62 183-4
• 7 Kwon B M, Lee S H, Kim K S, Lee I R, Lee U C, Hong S H, Bok S H. Rhombenone: farnesyl transferase inhibitor from the leaves of Hedera rhombea Bean.  Bioorg Med Chem Letters. 1997;  7 971-4
• 8 Kuo S M. Dietary flavonoid and cancer prevention: evidence and potential mechanism.  Crit Rev Oncog. 1997;  8 47-69
• 9 Maldonado E, Ortega A. Neo-clerodane diterpenes from Salvia thymoides .  Phytochemistry. 1997;  46 1249-54
• 10 Bosabalidis A, Gabrieli C, Niopas I. Flavone aglycones in glandular hairs of Origanum × intercedens .  Phytochemistry. 1998;  49 1549-54
• 11 Marco J A, Barbera O, Rodriguez S a, Domingo C, Adell J. Flavonoids and other phenolics from Artemisia hispanica .  Phytochemistry. 1998;  27 3155-60
• 12 Fan Y, Xing-Cong L, Han-Qing W, Chong-Ren Y. Flavonoid glycosides from Colebrookea oppositifolia .  Phytochemistry. 1996;  42 867-9
• 13 Nakasugi T, Komai K. Antimutagens in the Brazilian folk medicinal plant Carqueja (Baccharis trimera Less.)  J Agric Food Chem. 1998;  46 2560-4
• 14 Kim H M, Han S B, Kim M S, Kang J S, Oh G T, Hong D H. Efficient fixation procedure of human leukemia cells in sulforhodamine B cytotoxicity assay.  J Pharmacol Toxicol Methods. 1996;  36 163-9
• 15 Kwon B M, Lee S H, Cho Y K, Bok S H. Synthesis and biological activity of cinnamaldehydes as angiogenesis inhibitors.  Bioorg Med Chem Letters. 1997;  7 2473-6
• 16 Nakasugi T, Nakashima M, Komai K. Antimutagens in Gaiyou.  J Agric Food Chem. 2000;  48 3256-66
• 17 Schinella G R, Giner R M, Recio M C, Mordujovich de Buschiazz P, Rios J L, Manez S. Anti-inflammatory effects of South American Tanacetum vugare .  J Pharm Pharmacol. 1998;  50 1069-74
• 18 Colic M, Pavelic K. Molecular mechanisms of anticancer activity of natural dietetic products.  J Mol Med. 2000;  78 333-6
• 19 Cui B, Lee Y H, Chai H, Tucker J C, Fairchild C R,. et al . Cytotoxic sesquiterpenoids from Ratibida columnifera .  J Nat Prod. 1999;  62 1545-50
• 20 Fotsis T, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R, Schweigerer L. Genistein, a dietary-derived inhibitor of in vitro angiogenesis.  Proc Natl Acad Sci USA. 1993;  90 2690-4