Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor.

Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor.
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DOI:
10.3390/molecules22030474
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发表时间:
2017-03-16
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Tarpin M
Tarpin M
中科院分区:
其他
文献类型:
--
作者:
Nivelle L;Hubert J;Courot E;Jeandet P;Aziz A;Nuzillard JM;Renault JH;Clément C;Martiny L;Delmas D;Tarpin M

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在本研究中,白藜芦醇和各种低聚衍生物,从14 L生物反应器培养的引发葡萄藤细胞悬浮液(葡萄属labrusca L.)。从培养基中获得的粗乙酸乙酯芪提取物通过离心分配色谱法(CPC)使用梯度洗脱法进行分级分离,并随后通过使用基于13 C-NMR的去复制程序和进一步的2D NMR分析(包括HSQC、HMBC和COSY)鉴定了级分中所含的主要芪。除δ-viniferin(2)、leachianol F(4)和G(4′)外,(白藜芦醇(1)、ε-葡萄苷(5)、pallidol(3)和新表征的二聚体(6))以足够量的纯化合物形式回收,以允许评估它们对三种不同细胞系的细胞生长的生物活性,包括两种人皮肤恶性黑色素瘤癌细胞系(HT-144和SKMEL-28)和健康人真皮成纤维细胞HDF系。在本研究中获得的二聚体中,新表征的白藜芦醇二聚体(6)在自然界中从未被描述过,其生物学潜力在此首次进行了评估。ε-葡萄糖苷以及二聚体(6)对三种测试细胞系的IC 50值低于白藜芦醇和pallidol所产生的IC 50值。然而,前两个化合物的活性显着下降,在胎牛血清的存在下,虽然白藜芦醇和苍白球没有。白藜芦醇对健康和癌症细胞系的不同肿瘤活性也进行了讨论。
In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.). The crude ethyl acetate stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography (CPC) using a gradient elution method and the major stilbenes contained in the fractions were subsequently identified by using a 13C-NMR-based dereplication procedure and further 2D NMR analyses including HSQC, HMBC, and COSY. Beside δ-viniferin (2), leachianol F (4) and G (4′), four stilbenes (resveratrol (1), ε-viniferin (5), pallidol (3) and a newly characterized dimer (6)) were recovered as pure compounds in sufficient amounts to allow assessment of their biological activity on the cell growth of three different cell lines, including two human skin malignant melanoma cancer cell lines (HT-144 and SKMEL-28) and a healthy human dermal fibroblast HDF line. Among the dimers obtained in this study, the newly characterized resveratrol dimer (6) has never been described in nature and its biological potential was evaluated here for the first time. ε-viniferin as well as dimer (6) showed IC50 values on the three tested cell lines lower than the ones exerted by resveratrol and pallidol. However, activities of the first two compounds were significantly decreased in the presence of fetal bovine serum although that of resveratrol and pallidol was not. The differential tumor activity exerted by resveratrol on healthy and cancer lines was also discussed.
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