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黑色素瘤细胞的细胞毒性机制及两种巴西无刺蜂蜂胶的 UPLC-QTOF/MS 化学表征:哌啶生物碱的罕见存在。

Cytotoxicity mechanisms in melanoma cells and UPLC-QTOF/MS chemical characterization of two Brazilian stingless bee propolis: Uncommon presence of piperidinic alkaloids.

机构信息

Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.

Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.

出版信息

J Pharm Biomed Anal. 2018 Feb 5;149:502-511. doi: 10.1016/j.jpba.2017.11.038. Epub 2017 Nov 12.

Abstract

The present study characterized propolis extracts produced by Scaptotrigona bipunctata (Tubuna) and Melipona quadrifasciata (Mandaçaia) by LC-MS/MS; their cytotoxicity as well as the mechanism of action in a melanoma cellular model were also assessed. The chemical characterization performed by UPLC-ESI-QTOF/MS analysis revealed uncommon presence of piperidinic alkaloids in Tubuna's propolis extract together with C-glycopyranoside flavonoids. Mandaçaia's propolis collected in the same area rather presented terpenoids and flavonoids. Regarding the mechanism of cytotoxicity, propolis extracts increased the accumulation of reactive oxygen species (ROS), reduced the potential of mitochondrial membrane, induced a decrease in the proteins Bcl-2 and AKT-3 levels, and decreased melanoma cells' migration and invasion. Both propolis extracts induced apoptosis while only Mandaçaia's propolis extract induced cell cycle arrest in G2/M.

摘要

本研究通过 LC-MS/MS 对 Scaptotrigona bipunctata (Tubuna) 和 Melipona quadrifasciata (Mandaçaia) 产生的蜂胶提取物进行了表征;还评估了它们在黑素瘤细胞模型中的细胞毒性及其作用机制。通过 UPLC-ESI-QTOF/MS 分析进行的化学表征显示,Tubuna 蜂胶提取物中存在不常见的哌啶生物碱,以及 C-糖苷黄酮类化合物。在同一地区采集的 Mandaçaia 蜂胶则含有萜烯类化合物和黄酮类化合物。关于细胞毒性的作用机制,蜂胶提取物增加了活性氧(ROS)的积累,降低了线粒体膜的潜能,诱导 Bcl-2 和 AKT-3 蛋白水平下降,并减少了黑素瘤细胞的迁移和侵袭。两种蜂胶提取物均诱导细胞凋亡,而只有 Mandaçaia 的蜂胶提取物诱导细胞周期停滞在 G2/M。

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