Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Brazil.
J Pharm Pharmacol. 2017 Nov;69(11):1625-1633. doi: 10.1111/jphp.12789. Epub 2017 Aug 4.
The effects of propolis and phenolic compounds (caffeic acid - Caf; dihydrocinnamic acid - Cin; p-coumaric acid - Cou) in the same quantity found in our propolis sample were investigated on human laryngeal epidermoid carcinoma (HEp-2) cells.
Cell viability, apoptosis/necrosis and cell cycle arrest, P53 and CASPASE-3 gene expression, generation of reactive oxygen species (ROS) and the ability of propolis to induce doxorubicin (DOX) efflux using a P-glycoprotein (P-gp) inhibitor (verapamil) were assayed.
Propolis exerted a cytotoxic effect on HEp-2 cells, whereas isolated compounds had no effect on cell viability. Higher concentrations were tested and Caf induced late apoptosis or necrosis in HEp-2 cells, while propolis induced apoptosis, both probably due to ROS generation. P53 expression was downregulated by propolis but not by Caf. CASPASE-3 expression was correlated with induction of both early and late apoptosis, with both propolis and Caf alone upregulating its expression. Propolis induced cell cycle arrest at G2/M phase and Caf at S phase. Propolis but not Caf may act as a P-gp inhibitor by modulating P-gp activity and inhibiting DOX efflux.
Propolis exerted cytotoxic effects on HEp-2 cells, and the mechanisms are discussed, showing its potential as an antitumour drug.
研究与我们蜂胶样品中含量相同的蜂胶和酚类化合物（咖啡酸-Caf；肉桂酸-Cin；对香豆酸-Cou）对人喉表皮样癌细胞（HEp-2）的影响。
检测细胞活力、细胞凋亡/坏死和细胞周期停滞、P53 和 CASPASE-3 基因表达、活性氧（ROS）生成以及蜂胶诱导多柔比星（DOX）外排的能力，使用 P 糖蛋白（P-gp）抑制剂（维拉帕米）。
蜂胶对 HEp-2 细胞具有细胞毒性作用，而分离出的化合物对细胞活力没有影响。测试了更高的浓度，Caf 在 HEp-2 细胞中诱导晚期凋亡或坏死，而蜂胶诱导凋亡，这可能是由于 ROS 的产生。蜂胶下调 P53 表达，但 Caf 没有。CASPASE-3 表达与早期和晚期凋亡的诱导相关，蜂胶和 Caf 单独上调其表达。蜂胶诱导细胞周期停滞在 G2/M 期，Caf 诱导 S 期。蜂胶而不是 Caf 可能通过调节 P-gp 活性和抑制 DOX 外排来作为 P-gp 抑制剂。
蜂胶对 HEp-2 细胞具有细胞毒性作用，并对其机制进行了讨论，显示了其作为抗肿瘤药物的潜力。
