Lycorine, the main phenanthridine Amaryllidaceae alkaloid, exhibits significant antitumor activity in cancer cells that display resistance to proapoptotic stimuli: an investigation of structure-activity relationship and mechanistic insight.
Lycorine, the main phenanthridine Amaryllidaceae alkaloid, exhibits significant antitumor activity in cancer cells that display resistance to proapoptotic stimuli: an investigation of structure-activity relationship and mechanistic insight.
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DOI：
10.1021/jm901031h
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发表时间：
2009-10-22
影响因子：
7.3
通讯作者：
Evidente A
中科院分区：
文献类型：
--
作者：
Lamoral-Theys D;Andolfi A;Van Goietsenoven G;Cimmino A;Le Calvé B;Wauthoz N;Mégalizzi V;Gras T;Bruyère C;Dubois J;Mathieu V;Kornienko A;Kiss R;Evidente A
采用4种对促凋亡刺激具有不同程度抗性的癌细胞系和2种对促凋亡刺激敏感的癌细胞系，研究了22种石蒜碱相关化合物的体外抗肿瘤活性。石蒜碱及其六种同系物在个位数微摩尔范围内表现出效力，而没有化合物比石蒜碱更有活性。石蒜碱还显示出最高的潜在（体外）治疗比率，对癌症的活性至少是正常细胞的15倍。我们的研究还表明，石蒜碱通过细胞抑制作用而不是细胞毒性作用发挥其体外抗肿瘤活性。此外，石蒜碱在无毒性剂量下对移植B16F10黑色素瘤模型脑的小鼠有显著的治疗效果。因此，目前的研究结果使石蒜碱成为能够对抗癌症的化合物的优秀先导，这些癌症天然抵抗促凋亡刺激，如胶质母细胞瘤、黑色素瘤、非小细胞肺癌、转移性癌症等。
Twenty-two lycorine-related compounds were investigated for in vitro anti-tumor activity using four cancer cell lines displaying different levels of resistance to pro-apoptotic stimuli and two cancer cell lines sensitive to pro-apoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro anti-tumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at non-toxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to pro-apoptotic stimuli, such as glioblastoma, melanoma, non-small-cell-lung cancers, metastatic cancers, among others.
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影响因子：
10.6
作者：
Debeir, O;Van Ham, P;Decaestecker, C
通讯作者：
Decaestecker, C
影响因子：
3.8
作者：
EVIDENTE, A;CICALA, MR;ARRIGONI, O
通讯作者：
ARRIGONI, O
影响因子：
4.8
作者：
Dumont, Patrick;Ingrassia, Laurent;Kiss, Robert
通讯作者：
Kiss, Robert
影响因子：
3.8
作者：
Evidente, A;Andolfi, A;Motta, A
通讯作者：
Motta, A
影响因子：
64.8
作者：
ARRIGONI, O;LISO, RA;CALABRESE, G
通讯作者：
CALABRESE, G