Anti-Angiogenic and Anti-Tumor Activities of Isoflavonoids from the Rhizomes of Belamcanda chinensis

Abstract

The present study was carried out to clarify whether tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis (Iridaceae) inhibit angiogenesis by the experimental methods in vitro and in vivo. Tectorigenin and tectoridin decreased angiogenesis of both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Both compounds also reduced the proliferation of calf pulmonary arterial endothelial (CPAE) cells and found to possess relatively weak gelatinase/collagenase inhibitory activity in vitro. Tectorigenin exhibited a much stronger anti-proliferative activity than its glycoside, tectoridin and was almost equipotent to that of genistein, a reference drug. Tectorigenin, when administered subcutaneously at the dose of 30 mg/kg for 20 days to mice implanted with murine Lewis lung carcinoma (LLC), caused a significant inhibition of tumor volume by 30.8 %. Tectorigenin and tectoridin, when treated i. p. at the same dosage for 10 days to ICR mice bearing sarcoma 180, caused a significant suppression in tumor weight by 44.2 and 24.8 %, respectively.

Key words

Belamcanda chinensis - Iridaceae - isoflavonoids - tectorigenin - anti-angiogenesis - anti-tumor

References

• 1 Hyder S M, Stancel G M. Regulation of angiogenic growth factors in the female reproductive tract by estrogens and progestins.  Mol Endocrinol. 1999;  13 806-11
• 2 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease.  Nat Med. 1995;  1 27-31
• 3 Koch A E. Review: angiogenesis: implications for rheumatoid arthritis.  Arthritis Rheum. 1998;  41 951¯62
• 4 Ferrara N, Alitalo K. Clinical applications of angiogenic growth factors and their inhibitors.  Nat Med. 1999;  5 1359-64
• 5 Powell J. Update on hemangiomas and vascular malformations.  Curr Opin Pediatr. 1999;  11 457-63
• 6 Hanahan D. A flanking attack on cancer.  Nat Med. 1998;  4 13-4
• 7 Dubois R N, Abramson S B, Crofford L, Gupta R A, Simon L S, Van De Putte L B, Lipsky P E. Cyclooxygenase in biology and disease.  FASEB J. 1998;  12 1063-73
• 8 Williams C S, Smalley W, DuBois R N. Aspirin use and potential mechanisms for colorectal cancer prevention.  J Clin Invest. 1997;  100 1325-9
• 9 Yamaki M, Kato T, Kashihara M, Takagi S. Isoflavones from Belamcanda chinensis .  Planta Med. 1990;  56 335
• 10 Kim Y P, Yamada M, Lim S S, Lee S H, Ryu N, Shin K H, Ohuchi K. Inhibition by tectorigenin and tectoridin of prostaglandin E₂ production and cyclooxygenase-2 induction in rat peritoneal macrophages.  Biochim Biophys Acta. 1999;  10 399-407
• 11 Shin K H, Kim Y P, Lim S S, Lee S, Ryu N, Yamada M, Ohuchi K. Inhibition of prostaglandin E₂ production by the isoflavones tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis .  Planta Med. 1999;  65 776-7
• 12 Oikawa T, Hirotani K, Ogasawara H, Katayama T, Nakamura O, Iwaguchi T, Hiragun A. Inhibition of angiogenesis by vitamin D₃ analogue.  Eur J Pharmacol. 1990;  178 247-50
• 13 Suh H S, Jung E J, Kim T H, Kim K W. Anti-angiogenic activity of ursodeoxycholic acid and its derivatives.  Cancer Lett. 1997;  113 117-22
• 14 Denholm E M, Lin Y Q, Silver P J. Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of angiogenesis, proliferation and invasion.  Eur J Pharmacol. 2001;  416 213-21
• 15 Passanti A, Taylor R M, Pili R, Guo Y, Long P V, Haney J A, Paulay P R, Grant D S, Martin G R. Simple and quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor.  Lab Invest. 1992;  69 519-28
• 16 O' Reilly M S, Holmgren L, Shing Y, Chen C, Rosenthal R A, Moses M, Lane W S, Cao Y, Sage E H, Folkman J. A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.  Cell. 1994;  79 315-28
• 17 Fotsis T, Pepper M S, Aktas E, Breit S, Rasku S, Adlercreutz H, Wahala K, Montesano R, Schweigerer L. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis.  Cancer Res. 1997;  57 2916-21
• 18 Akarasereenont P, Mitchell J A, Appleton I, Thiemermann C, Vane J R. Involvement of tyrosine kinase in the induction of cyclo-oxygenase and nitric oxide synthase by endotoxin in cultured cells.  Br J Pharmacol. 1994;  113 1522-8
• 19 Fotsis J, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R, Schweigerer L. Genistein, a dietary-derived inhibitor of in vitro angiogenesis.  Proc Nat Acad Sci. 1993;  90 2690-4
• 20 Lee K T, Sohn I C, Kim Y K, Choi J H, Choi J W, Park H J, Itoh Y, Miyamoto K. Tectorigenin, an isoflavone of Pueraria thunbergiana Benth., induces differentiation and apoptosis in human promyelocytic leukemia HL-60 cells.  Biol Pharm Bull. 2001;  24 1117-21