Cancer Chemopreventive Activity of Terpenoid Coumarins from Ferula Species

Abstract

Several natural products have been found to have anti-tumor promoting activity. In the present study, we carried out a primary screening of ten terpenoid coumarins isolated from plants of the Ferula species, examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. Auraptene (7-geranyloxycoumarin, 1) and umbelliprenin (7-farnesyloxycoumarin, 2) were found to significantly inhibit EBV-EA activation and preserved the high viability of Raji cells, suggesting that they might be valuable anti-tumor-promoting agents (IC₅₀ 8.3 and 9.1 nM, respectively). Our findings revealed that the presence of a prenyl moiety in the terpenoid coumarins plays an important role in anti-tumor promoting activity as previously reported for xanthones, coumarins, flavonoids and phenylpropanoids.

Apiaceae - Ferula - anti-tumor promoting effect - terpenoid coumarins - Epstein-Barr virus activation assay - cancer chemoprevention

References

• 1 Ahmed A A. Sesquiterpene coumarins and sesquiterpenes from Ferula sinaica.  Phytochemistry. 1999;  50 109-12
• 2 Ahmed A A, Abd El-Razek M H, Nassar M I, Izuma S, Ohta S, Hirata T. Sesquiterpene coumarins from the roots of Ferula assafoetida.  Phytochemistry. 2001;  58 1289-95
• 3 Valle G M, Appendino G, Nano G M, Picci V. Prenylated coumarins and sesquiterpenoids from Ferula communis.  Phytochemistry. 1987;  26 253-8
• 4 Iranshahi M, Arfa P, Ramezani M, Jaafari M R, Sadeghian H, Bassarello C. et al . Sesquiterpene coumarins from Ferula szowitsiana and in vitro antileishmanial activity of 7-prenyloxycoumarins against promastigotes.  Phytochemistry. 2007;  68 554-61
• 5 Saleem M, Alam A, Sultana S. Asafoetida inhibits early events of carcinogenesis: A chemopreventive study.  Life Sci. 2001;  68 1913-21
• 6 Rajanikanth B, Ravindranath B, Shankaranaryana M L. Volatile polysulphides of asafoetida.  Phytochemistry. 1984;  23 899-900
• 7 Kajimoto T, Yahiro K, Nohara T. Sesquiterpenoid and disulphide derivatives from Ferula assafoetida.  Phytochemistry. 1989;  28 1761-3
• 8 Ito C, Itoigawa M, Furukawa H, Tokuda H, Okuda Y, Mukainaka T. et al . Anti-tumor-promoting effects of 8-substituted 7-methoxycoumarins on Epstein-Barr virus assay.  Cancer Lett. 1999;  138 87-92
• 9 Iranshahi M, Amin G h, Shafiee A. A new coumarin from Ferula persica.  Pharm Biol. 2004;  42 440-2
• 10 Abd El-Razek M H, Ohta S, Hirata T. Terpenoid coumarins of the genus Ferula.  Heterocycles. 2003;  60 689-716
• 11 Lee E, Mabry T J. Sesquiterpene coumarin ethers of Ferula tingitana.  J Nat Prod. 1985;  48 326-7
• 12 Ito C, Itoigawa M, Furukawa H, Rao K S, Enjo F, Bu P. et al . Xanthones as inhibitors of Epstein-Barr virus activation.  Cancer Lett. 1998;  132 113-7
• 13 Ito C, Itoigawa M, Tan H TW, Tokuda H, Mou X Y, Mukainaka T. et al . Anti-tumor promoting effects of isoflavonoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.  Cancer Lett. 2000;  152 187-92
• 14 Itoigawa M, Ito C, Tokuda H, Enjo F, Nishino H, Furukawa H. Cancer chemopreventive activity of phenylpropanoids and phytoquinoids from Illicium plants.  Cancer Lett. 2004;  214 165-9
• 15 Curini M, Cravotto G, Epifano F, Giannone G. Chemistry and biological activity of natural and synthetic prenyloxycoumarins.  Curr Med Chem. 2006;  13 199-222
• 16 Bertram J S, Kolonel L N, Meyskens F L. Rationale and strategies for chemoprevention of cancer in humans.  Cancer Res. 1987;  47 3012-31
• 17 Grabley S, Thiericke R. Drug discovery from nature, first edition. London; Springer 1999: 96
• 18 Shahverdi A R, Saadat F, Khorramizadeh M R, Iranshahi M, Khoshayand M R. Two matrix metalloproteinase inhibitors from Ferula persica var. persica.  Phytomedicine. 2006;  13 712-7