背景：胰腺癌是全球癌症相关死亡的主要原因，并且全球发病率不断增加。我们之前报道过马桑乙醇提取物（RCE）对三阴性乳腺癌和结肠癌细胞的抗癌作用。在此，我们研究了 RCE 对人胰腺癌细胞的抗癌作用。方法：使用 Cell Titer-Glo 测量细胞活力，并根据两种 DNA 结合染料的不同渗透性对活细胞和死细胞进行染色。细胞周期分布和膜联蛋白V染色在Muse细胞分析仪中进行。通过蛋白质印迹测定蛋白质水平。通过卵内鸡胚绒毛尿囊膜测定评估肿瘤生长。结果：我们发现 RCE 显着抑制胰腺癌细胞（Panc-1、Mia-PaCa-2、S2-013、AsPC-1）的活力和集落生长。 RCE 在胰腺癌细胞（Panc-1 和 Mia-PaCa-2）中的抗增殖作用是通过诱导 G1 细胞周期停滞、不依赖 Beclin-1 的自噬和细胞凋亡来介导的。 RCE 激活细胞凋亡的外在和内在途径并调节 Bax/Bcl-2 凋亡开关。从机制上讲，我们发现 RCE 抑制 AKT/mTOR 通路，在该通路下游，观察到细胞周期调节因子 p70S6K 失活和抗凋亡蛋白 survivin 下调。此外，我们发现 RCE 诱导的自噬先于细胞凋亡。此外，我们在鸡胚异种移植模型中证实了RCE的抗癌作用，发现RCE抑制胰腺癌异种移植物的生长而不影响胚胎存活。结论：总的来说，我们的研究结果表明，马桑通过细胞周期损伤、自噬和细胞凋亡发挥有效的抗胰腺癌活性，因此是抗癌植物化学物质的有前途的来源。版权所有 © 2024 El Mahi, Nizami, Wali, Al Neyadi,马格拉马内、阿扎尼、阿拉法特、阿图布、开斋节和伊拉特尼。

Background:Pancreatic cancer is a leading cause of cancer-related mortality worldwide with increasing global incidence. We previously reported the anticancer effect of Rhus coriaria ethanolic extract (RCE) in triple negative breast and colon cancer cells. Herein, we investigated the anticancer effect of RCE on human pancreatic cancer cells. Methods: Cell viability was measured using Cell Titer-Glo and staining of viable and dead cells based on differential permeability to two DNA binding dyes. Cell cycle distribution and annexin V staining was carried out in Muse cell analyzer. Protein level was determined by Western blot. Tumor growth was assessed by in ovo chick embryo chorioallantoic membrane assay. Results: We found that RCE significantly inhibited the viability and colony growth of pancreatic cancer cells (Panc-1, Mia-PaCa-2, S2-013, AsPC-1). The antiproliferative effects of RCE in pancreatic cancer cells (Panc-1 and Mia-PaCa-2) were mediated through induction of G1 cell cycle arrest, Beclin-1-independent autophagy, and apoptosis. RCE activated both the extrinsic and intrinsic pathways of apoptosis and regulated the Bax/Bcl-2 apoptotic switch. Mechanistically, we found that RCE inhibited the AKT/mTOR pathway, downstream of which, inactivation of the cell cycle regulator p70S6K and downregulation of the antiapoptotic protein survivin was observed. Additionally, we found that RCE-induced autophagy preceded apoptosis. Further, we confirmed the anticancer effect of RCE in a chick embryo xenograft model and found that RCE inhibited the growth of pancreatic cancer xenografts without affecting embryo survival. Conclusion: Collectively, our findings demonstrate that Rhus coriaria exerts potent anti-pancreatic cancer activity though cell cycle impairment, autophagy, and apoptosis, and is hence a promising source of anticancer phytochemicals.Copyright © 2024 El Mahi, Nizami, Wali, Al Neyadi, Magramane, Al Azzani, Arafat, Attoub, Eid and Iratni.