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In vitro and In vivo Antiproliferative Effect of a Combination of Ultraviolet‐A and Alkoxy Furocoumarins Isolated from Umbelliferae Medicinal Plants, in Melanoma Cells
Author(s) -
Kimura Yoshiyuki,
Sumiyoshi Maho,
Sakanaka Masahiro,
Taniguchi Masahiko,
Baba Kimiye
Publication year - 2013
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12122
Subject(s) - furocoumarins , chemistry , in vivo , alkoxy group , furocoumarin , in vitro , melanoma , cell growth , cell cycle , pharmacology , apoptosis , biochemistry , biology , cancer research , dna , organic chemistry , alkyl , microbiology and biotechnology , photochemistry
We examined the effects of six furocoumarins with alkoxy groups at the C‐5 or C‐8 position isolated from Umbelliferae medicinal plants on cell proliferation, and their mechanisms of action against B16F10 melanoma cells or in melanin‐possessing hairless mice implanted with B16F10 cells, under UVA irradiation. Three furocoumarins with an alkoxy group at C‐5, isoimperatorin (1), oxypeucedanin (2) and oxypeucedanin hydrate (3), showed antiproliferative activity and caused G 2 /M arrest at concentrations of 0.1–10.0 μ m . Furthermore, three furocoumarins with an alkoxy group at C‐8, imperatorin (4), heraclenin (5) and heraclenol (6), inhibited the proliferation of melanoma cells and cell cycle at G 2 /M at concentrations of 0.1–1.0 μ m . UVA plus 1, 2, 3, 4 and 6 reduced tumor growth and final tumor weight in B16F10‐bearing mice at a dose of 0.3, 0.5 or 1.0 mg kg −1 (intraperitoneal injection). UVA plus 1, 3 and 6 increased Chk1 phosphorylation and reduced cdc2 (Thr 161) phosphorylation in melanoma cells. We suggest that the antitumor actions of UVA plus furocoumarins with an alkoxy group at C‐5 or C‐8 were due to G 2 /M arrest of the cell cycle by an increase in phosphor‐Chk1 and decrease in phospho‐cdc2.