Carvacrol is a Novel Natural Therapeutic Approach Through the Inhibition of Proliferation, Autophagy and Migration in Pancreatic Ductal Adenocarcinoma Cells

Objective: Pancreatic ductal adenocarcinoma, which is the most common and aggressive pancreatic cancer, has the highest mortality rate of cancers because of difficulties in diagnosis and chemoresistance. As the chemotherapeutic options are very limited and insufficient for PDAC, novel effective therapeutic approaches are urgently needed for pancreatic cancer patients. Carvacrol naturally found in thyme (Thymus vulgaris), wild bergamot (Citrus aurantium var. bergamia Loisel), black cumin (Nigella sativa), marjoram (Origanum scabrum, Origanum microphyllum, Origanum onites, Origanum vulgare) and black pepper (Lepidium flavum) plants is shown to have antibacterial and antioxidant effects. In this study, we aimed to investigate the anticarcinogenic potential of carvacrol through proliferation and autophagy in PDAC cells. Material and Method: To determine the anti-proliferative effects of carvacrol in Panc-1 cells, we performed the MTS assay using different carvacrol doses of 100, 200, 300, 400, 500, 600, 700 and 800 μM at 24h, 48h, 72h. The gene and protein expressions of Atg16L1 and Beclin-1, autophagy key mediators, were analyzed by RT-PCR and western blot in Panc-1 cells treated with 300 and 400 μM for 24h, 48h. Additionally, the migrative property of PDAC cells was evaluated using a wound healing assay. Results: Based on MTS results, carvacrol significantly inhibited cell proliferation in the doses of 300 and 400 μM at 24h and 48 h in Panc-1. These same doses led to decreased autophagy and migration through Atg16L1, and Beclin-1 expressions. Conclusion: Our findings first revealed that carvacrol has promising value as a potential therapeutic approach for PDAC. We believe that further mechanistic investigations will be a guide for its clinical usage.