Elkady Ayman I
Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Anticancer Agents Med Chem. 2018;18(2):216-236. doi: 10.2174/1871520617666170725165717.
Prostate cancer-associated mortality is increasing at an alarming rate, which highlights the inevitability for unearthing novel agent for the management of this disease. Anethole, a major constituent of Foeniculum vulgare (fennel) essential oil, is widely used in folk medicine; it possesses anti-oxidant, antiinflammatory, anti-proliferative and tumoricidal potentialities.
The current research was conducted to assess the impact of anethole on prostate cancer cell line, PC- 3, and to delineate the molecular mechanism of action.
To achieve this aim, the growth-inhibitory effect of anethole was evaluated by MTT assay. Apoptotic death and cell cycle analyses were assessed by flow cytometry and alterations in gene expression were investigated by qPCR and Western blot analyses.
The observations indicated that anethole inhibited proliferation, clonal growth and migration of PC-3 cells. It also suppressed growth of PC-3 derived cancer stem cells (tumorspheres). Pro-apoptotic potential of anethole was accompanied by generation of ROS, permeabilization of the mitochondrial and lysosomal membranes, activation of caspase-3 and -9, DNA damage, PARP cleavage and induction of Bax/Bcl-2 protein ratio. Further, anethole induced G2/M phase arrest, downregulation of cyclins D1, CDK-4 and c-Myc proteins and upregulation of p21 and p27. Anethole suppressed nuclear localization of NF-κB protein and downregulated transcription of NF-κB-dependent genes.
Overall, the above findings highlight the effectiveness of anethole as a potential candidate for prostate cancer therapy.
前列腺癌相关死亡率正以惊人的速度上升，这凸显了发掘治疗该疾病新药物的必要性。茴香脑是小茴香（Foeniculum vulgare）精油的主要成分，在民间医学中广泛使用；它具有抗氧化、抗炎、抗增殖和杀肿瘤潜力。
进行本研究以评估茴香脑对前列腺癌细胞系PC-3的影响，并阐明其分子作用机制。
为实现这一目标，通过MTT法评估茴香脑的生长抑制作用。采用流式细胞术评估凋亡死亡和细胞周期分析，并通过qPCR和蛋白质印迹分析研究基因表达的变化。
观察结果表明，茴香脑抑制PC-3细胞的增殖、克隆生长和迁移。它还抑制PC-3来源的癌症干细胞（肿瘤球）的生长。茴香脑的促凋亡潜力伴随着活性氧的产生、线粒体和溶酶体膜的通透性增加、半胱天冬酶-3和-9的激活、DNA损伤、聚ADP核糖聚合酶（PARP）裂解以及Bax/Bcl-2蛋白比值的诱导。此外，茴香脑诱导G2/M期阻滞，下调细胞周期蛋白D1、细胞周期蛋白依赖性激酶-4（CDK-4）和c-Myc蛋白，并上调p21和p27。茴香脑抑制核因子κB（NF-κB）蛋白的核定位，并下调NF-κB依赖性基因的转录。
总体而言，上述发现突出了茴香脑作为前列腺癌治疗潜在候选药物的有效性。
