Anethole attenuates lung cancer progression by regulating the proliferation and apoptosis through AKT and STAT3 signaling
2023
Venkata Kumar | Maddula Venkateswarulu
Background: The main constituent of fennel, anethole, exerts beneficial effects in many diseases, including antiproliferative and tumoricidal capacities. This study aimed to investigate the effect of anethole on the human non-small cell lung cancer (NSCLC) cell line, A549, and the related molecular mechanisms. Methods: The proliferation was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Apoptosis situation was determined using fluorescence-activated cell sorting and DNA fragmentation assay combined with immunoblotting assay probing-related protein expression. Phosphoinositide 3-kinases-protein kinase B (PI3K-AKT) and signal transducer and activator of transcription 3 (STAT3) signaling proteins were evaluated using immunoblotting. Xenograft model was constructed to determine the tumor volume and weight and to evaluate the expression of Ki67 via immunohistochemistry and cleaved caspase 3 via immunoblotting. Results: Anethole inhibited proliferation and clonal growth of A549 cells. The promotion of A549 cell apoptosis by anethole was evidenced by increased apoptotic ratio, abundant DNA fragments, and caspase-3 activation. Key proteins in PI3K-AKT and STAT3 signaling pathways were decreased in anethole group. Additionally, xenografted tumors in anethole group retarded with decreased Ki67 and increased cleaved caspase 3 expression. Conclusions: Anethole induced tumor cell apoptosis and retarded cell proliferation. AKT and STAT3 signaling pathways might be involved in the effects of anethole. Our findings highlight the feasibility of anethole in the treatment of lung cancer.
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