Khorsandi L, Orazizadeh M, Niazvand F, Abbaspour M R, Mansouri E, Khodadadi A
Bratisl Lek Listy. 2017;118(2):123-128. doi: 10.4149/BLL_2017_025.
This study investigated the quercetin (Que) effects on growth of MCF-7 human cancer breast cell line and its cellular death mechanism.
Quercetin has been found to be very efficacious against many different types of cancer cells. However, the study is not sufficiently powered to demonastrate anticancer mechanisms.
MCF-7cells were treated by 50 µM/ ml of Que for 48 hours. MCF-7 cells were also pretreated with 10 Μm ZVAD (apoptosis inhibitor) or 3 mM Nec-1 (necroptosis inhibitor) for evaluation of cell death induced by apoptosis or necroptosis.
MTT and clonogenicity assays revealed that the Que induced a significant increase in cell viability and proliferation in presence of Nec-1 in comparison to the presence of ZVAD (p < 0.05). Que also increased apoptosis as revealed by DAPI staining and morphology evaluations. Following Que treatment Bcl-2 expression was significantly decreased while Bax expression was significantly increased. Que in presence of Nec-1 decreased expression of Bax gene, reduced apoptotic index, increased cell viability and proliferation of MCF-7 cells in comparison to absence of Nec-1. MCF-7 cells showed a significantly increased expression of RIPK1 and RIPK3 in response to Que plus ZVAD in comparison to absence of ZVAD.
Our results revealed that the high Que toxicity for breast cancer cells depends on multiple cell death pathways, which involve mainly necroptosis (Fig. 6, Ref. 21).
本研究调查了槲皮素（Que）对MCF-7人乳腺癌细胞系生长的影响及其细胞死亡机制。
已发现槲皮素对许多不同类型的癌细胞非常有效。然而，该研究的力度不足以证明其抗癌机制。
用50μM/ml的Que处理MCF-7细胞48小时。还用10μM ZVAD（凋亡抑制剂）或3mM Nec-1（坏死性凋亡抑制剂）预处理MCF-7细胞，以评估凋亡或坏死性凋亡诱导的细胞死亡。
MTT和克隆形成试验表明，与存在ZVAD相比，在存在Nec-1的情况下，Que诱导细胞活力和增殖显著增加（p<0.05）。DAPI染色和形态学评估显示，Que也增加了细胞凋亡。Que处理后，Bcl-2表达显著降低，而Bax表达显著增加。与不存在Nec-1相比，在存在Nec-1的情况下，Que降低了Bax基因的表达，降低了凋亡指数，增加了MCF-7细胞的活力和增殖。与不存在ZVAD相比，MCF-7细胞在Que加ZVAD处理后RIPK1和RIPK3的表达显著增加。
我们的结果表明，Que对乳腺癌细胞的高毒性取决于多种细胞死亡途径，主要涉及坏死性凋亡（图6，参考文献21）。
