Anethole Inhibits the Proliferation of Human Prostate Cancer Cells via Induction of Cell Cycle Arrest and Apoptosis

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: Overall, the above findings highlight the effectiveness of anethole as a potential candidate for prostate cancer therapy.