-Anethole Abrogates Cell Proliferation and Induces Apoptosis through the Mitochondrial-Mediated Pathway in Human Osteosarcoma Cells.

-Anethole, the major bioactive component of Hook. commonly known as star anise exhibits various pharmacological activities including anti-inflammatory, antimicrobial, insecticidal, and antitumor. Osteosarcoma is an extremely aggressive malignant bone tumor that affects children and young adults and accounts for around 60% of all sarcomas. The study was planned to evaluate the potential of -Anethole against Human osteosarcoma cell line MG-63. The antiproliferative activity of -Anethole was assessed by MTT assay. -Anethole exhibited apoptotic cell death as monitored by confocal/electron microscopy and flow cytometry studies. Modulation of gene expression was studied by Western blot and RT-PCR analysis. The present study revealed that -Anethole inhibited osteosarcoma proliferation in a dose-dependent manner with a GI value of 60.25 µM and showed pro-apoptotic activity as analyzed by Annexin V-FITC/PI assay. Flow cytometric analysis revealed that -Anethole induced cell cycle arrest at the / phase with the generation of reactive oxygen species and reduction in mitochondrial membrane potential (). Immunoblotting results showed the increased expression of caspase-9/-3, p53, and decreased expression of Bcl-xL suggesting the involvement of the p53 and mitochondrial intrinsic pathway. This work provides a rationale that -Anethole might be considered as a promising chemotherapeutic/nutraceutical agent for the management of osteosarcoma.Highlights-Anethole inhibited cell growth and caused / arrest in Human osteosarcoma MG-63 cell line.-Anethole led to the loss of mitochondrial membrane permeability along with ROS generation.-Anethole upregulates the expression of p53, Caspase-9/-3, and downregulate Bcl-xL expression.