Anti-tumor effects of various furocoumarins isolated from the roots, seeds and fruits of Angelica and Cnidium species under ultraviolet A irradiation

Abstract

We examined the effects on cell proliferation of 10 methoxyfurocoumarins and 7 dihydrofurocumarins isolated from Umbelliferae medicinal plants, and their mechanisms of action against B16F10 melanoma cells or in melanin-possessing hairless mice implanted with B16F10 melanoma cells, under UVA irradiation. Furocoumarins having a methoxy group, such as bergapten (1), xanthotoxin (2), phellopterin (4), byakangelicin (6), neobyakangelicin (8), isobergapten (9) and sphondin (10), showed anti-proliferative activity and caused G2/M arrest at concentrations of 0.05-15.0 μM. The 7 dihydrofurocoumarins had no effect. UVA plus 1, 2, 4, 6 and sec-O-acetylbyakagelicin (7), having one methoxy group at the C-5 position and a linear-type conformation, reduced tumor growth and final tumor weight in B16F10-bearing mice at 0.5 or 1.0 mg/kg (intraperitoneal injection). UVA plus 1 and 2 increased Chk1 phosphorylation and decreased cdc2 (Thr 161) phosphorylation in the melanoma cells. The anti-tumor actions of UVA plus furocoumarins having a methoxy group might be due to the arrest of the cell cycle at G2/M through an increase in phospho-Chk1 and reduction in phospho-cdc2.