title: 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.
authors: Division of Functional Histology, Department of Functional Biomedicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors: Maho
authors: M
authors: Sumiyoshi
authors: Masahiro
authors: M
authors: Sakanaka
authors: Masahiko
authors: M
authors: Taniguchi
authors: Kimiye
authors: K
authors: Baba
authors: Yoshiyuki
authors: Y
authors: Kimura
mesh_terms: D029969:Angelica / Q000737:chemistry; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D031048:Cnidium / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D011564:Furocoumarins / Q000302:isolation & purification / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless; D011701:PUVA Therapy; D010766:Phosphorylation; D008517:Phytotherapy; D018517:Plant Roots; D010946:Plants, Medicinal; D011494:Protein Kinases / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000302:isolation & purification / Q000494:pharmacology*; D012639:Seeds; D047368:Tumor Burden / Q000187:drug effects; D014466:Ultraviolet Rays
chemical_list: D011564:Furocoumarins; D011838:Radiation-Sensitizing Agents; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; D016203:CDC2 Protein Kinase
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