Anti-tumor effects of various furocoumarins isolated from the roots, seeds and fruits of Angelica and Cnidium species under ultraviolet A irradiation
Anti-tumor effects of various furocoumarins isolated from the roots, seeds and fruits of Angelica and Cnidium species under ultraviolet A irradiation
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DOI：
10.1007/s11418-013-0774-z
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发表时间：
2014-01-01
影响因子：
3.3
通讯作者：
Kimura, Yoshiyuki
中科院分区：
文献类型：
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作者：
Sumiyoshi, Maho;Sakanaka, Masahiro;Kimura, Yoshiyuki
我们研究了从伞形科药用植物中分离的10种甲氧基呋喃香豆素和7种二氢呋喃香豆素对细胞增殖的影响，以及它们对B16 F10黑色素瘤细胞或在UVA照射下植入B16 F10黑色素瘤细胞的黑色素无毛小鼠中的作用机制。具有甲氧基的呋喃香豆素类，如佛手柑内酯（1）、花椒毒素（2）、苦蝶呤（4）、白当归素（6）、新白当归素（8）、异佛手柑内酯（9）和鞘氨醇（10），在0.05-15.0 μ M的浓度下显示出抗增殖活性并引起G2/M停滞。7种二氢呋喃香豆素类药物均无效。UVA加1，2，4，6和sec-O-acetylbyakagelicin（7），在C-5位有一个甲氧基和线性构象，在0.5或1.0 mg/kg（腹膜内注射）的荷B16 F10小鼠中减少肿瘤生长和最终肿瘤重量。UVA加1和2增加Chk 1磷酸化和减少cdc 2（Thr 161）的磷酸化在黑色素瘤细胞。UVA加具有甲氧基的呋喃香豆素的抗肿瘤作用可能是由于通过增加磷酸化-Chk 1和减少磷酸化-cdc 2将细胞周期阻滞在G2/M。
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 mu M. 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.