Anethole induces anti-oral cancer activity by triggering apoptosis, autophagy and oxidative stress and by modulation of multiple signaling pathways

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.

Assessment of Oxidative Stress and Inflammatory Markers of Medical Importance in Oral Squamous Cell Carcinoma

“…In our study all of the oxidative stress markers were significantly elevated as compared to healthy individual. Similarly, results were noted by K Babiuchet al and many other researchers (Babiuch et al, 2019;Bozan et al, 2018;Cherian et al, 2019;Contant et al, 2021). Interlukin-6 is a multifunctional cytokine having a wide range of immunological activities, and it is also a potential mediator in the cancer development.…”

Naproxen-Loaded Poly(2-hydroxyalkyl methacrylates): Preparation and Drug Release Dynamics

“…The human oral cancer cell line Ca9–22 cells were cultured at 37 °C and 5% CO 2 in RPMI-1640 medium (Thermo Fisher Scientific, Burlington, ON, Canada), supplemented with L-glutamine, 5% fetal bovine serum (FBS, Gibco) provided by the same company, and 1% penicillin/streptomycin solution (Sigma-Aldrich, Oakville, ON, Canada). Cell proliferation was bi-evaluated using two MTT and LDH tests as described by Semlali et al 2021 [ 35 , 36 ] and Contant et al 2021 [ 37 ]. For the MTT assay, 10 5 Ca9-22 cells per well containing the sample were seeded in 24-well plates for 24 h. After adhesion and growth of the cells, the culture medium is replaced by a new one containing a solution of MTT at 5 mg∙ml −1 in PBS and left for 3 h at 37 °C in the dark.…”

Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives

“…Examples of phenylpropanoids such as anethole, cinnamaldehyde, eugenol, isoeugenol, myristicin, safrole, and vanillin. In a recent study, anethole has been reported to yield anticancer activity ( Contant, Rouabhia, Loubaki, Chandad, & Semlali, 2021 ). Moreover, myristicin has been described to exert antiproliferative and anti-inflammatory properties ( Seneme, Dos Santos, Silva, Franco, & Longato, 2021 ) and safrole has been reported to promote diverse biological activities, such as antidiabetic, antimicrobial, analgesic, and antifungal activities ( Eid & Hawash, 2021 ).…”