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劳洛苷 B,一种来自月桂(月桂树)叶的巨型 aglycone 糖苷,通过抑制 NF-κB 激活诱导人黑色素瘤细胞系凋亡。

Lauroside B, a megastigmane glycoside from Laurus nobilis (bay laurel) leaves, induces apoptosis in human melanoma cell lines by inhibiting NF-κB activation.

机构信息

Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.

出版信息

J Nat Prod. 2011 Feb 25;74(2):228-33. doi: 10.1021/np100688g. Epub 2010 Dec 28.

DOI:10.1021/np100688g
PMID:21188975
Abstract

Malignant melanoma is a highly aggressive tumor that frequently resists chemotherapy, so the search for new agents for its treatment is of great importance. In the present study, the antiproliferative propensity against human melanoma cell lines of lauroside B (1), a megastigmane glycoside isolated from Laurus nobilis (bay laurel) leaves, was investigated. This compound suppressed the proliferation of three human melanoma cell lines, namely, A375, WM115, and SK-Mel-28. The 1-induced inhibition of human melanoma cell proliferation was due to the induction of apoptosis, as demonstrated by FACS analysis with annexin V/PI staining and confirmed by activation of caspase-3 and by the cleavage of poly(ADP-ribose) polymerase (PARP). Growing evidence implicates NF-κB as an important contributor to metastasis and increased chemoresistance of melanoma. Thus, it was hypothesized that 1-induced apoptosis could be associated with suppression of NF-κB activation. The results showed that exposure of human melanoma cells to 1 inhibited IκB-α degradation and constitutive NF-κB DNA-binding activity as well as the expression, regulated by NF-κB, of two antiapoptotic genes, XIAP and c-FLIP. Induction of apoptosis by 1 in human aggressive melanoma cell lines has a potential high biological value.

摘要

恶性黑色素瘤是一种高度侵袭性肿瘤,经常对化疗产生耐药,因此寻找新的治疗药物非常重要。本研究旨在探讨从月桂叶中分离得到的megastigmane 糖苷 lauroside B(1)对人黑色素瘤细胞系的抗增殖作用。该化合物抑制了三种人黑色素瘤细胞系 A375、WM115 和 SK-Mel-28 的增殖。流式细胞术分析 Annexin V/PI 染色证实,1 诱导的人黑色素瘤细胞增殖抑制是由于细胞凋亡的诱导,这一结果得到了 caspase-3 激活和多聚(ADP-核糖)聚合酶(PARP)切割的证实。越来越多的证据表明 NF-κB 是黑色素瘤转移和化疗耐药性增加的重要因素。因此,假设 1 诱导的细胞凋亡可能与抑制 NF-κB 激活有关。结果表明,1 处理人黑色素瘤细胞可抑制 IκB-α 降解和 NF-κB 的组成性 DNA 结合活性,以及 NF-κB 调控的两种抗凋亡基因 XIAP 和 c-FLIP 的表达。1 在人侵袭性黑色素瘤细胞系中诱导细胞凋亡具有潜在的高生物学价值。

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