RRC ID 65941
Author Contant C, Rouabhia M, Loubaki L, Chandad F, Semlali A.
Title Anethole induces anti-oral cancer activity by triggering apoptosis, autophagy and oxidative stress and by modulation of multiple signaling pathways.
Journal Sci Rep
Abstract Oral cancer is one of the major public health problems. The aim of this study was to evaluate the effects of anethole, 1-methoxy-4-[(E)-1-propenyl]-benzene, on growth and apoptosis of oral tumor cells, and to identify the signaling pathways involved in its interaction with these cancer cells. Cancer gingival cells (Ca9-22) were treated with different concentrations of anethole. Cell proliferation and cytotoxic effects were measured by MTT and LDH assays. Cell death, autophagy and oxidative stress markers were assessed by flow cytometry while cell migration was determined by a healing capacity assay. The effect of anethole on apoptotic and pro-carcinogenic signaling pathways proteins was assessed by immunoblotting. Our results showed that anethole selectively and in a dose-dependent manner decreases the cell proliferation rate, and conversely induces toxicity and apoptosis in oral cancer cells. This killing effect was mediated mainly through NF-κB, MAPKinases, Wnt, caspase 3, 9 and PARP1 pathways. Anethole showed an ability to induce autophagy, decrease reactive oxygen species (ROS) production and increased intracellular glutathione (GSH) activity. Finally, anethole treatment inhibits the expression of oncogenes (cyclin D1) and up-regulated cyclin-dependent kinase inhibitor (p21WAF1), increases the expression of p53 gene, but inhibits the epithelial-mesenchymal transition markers. These results indicate that anethole could be a potential molecule for the therapy of oral cancer.
Volume 11(1)
Pages 13087
Published 2021-6-22
DOI 10.1038/s41598-021-92456-w
PII 10.1038/s41598-021-92456-w
PMID 34158560
PMC PMC8219795
MeSH Allylbenzene Derivatives / pharmacology* Anisoles / pharmacology* Antineoplastic Agents / pharmacology Apoptosis / drug effects Autophagy / drug effects Cell Death / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Cell Survival / drug effects Drug Screening Assays, Antitumor / methods Humans Mouth Neoplasms / drug therapy* Oxidative Stress / drug effects Reactive Oxygen Species / metabolism Signal Transduction / drug effects
IF 3.998
Human and Animal Cells Ca9-22(RCB1976)