Catechol enhances chemo- and radio-sensitivity by targeting AMPK/Hippo signaling in pancreatic cancer cells

Overcoming chemo- and radio-resistance is a major challenge in pancreatic cancer treatment. Therefore, there is an urgent need to discover novel therapeutic approaches to avoid chemo- and radio-resistance in pancreatic cancer. Catechol is a phytochemical found in some fruits and vegetables. A few studies have reported on the potential anticancer effects of pure catechol. The present study aimed to explore the chemo- and radio-sensitizing effects of catechol in Panc-1 human pancreatic cancer cells. The effects of catechol on Panc-1 cell proliferation, clonogenic survival, invasion, and migration were assessed using MTT, cell migration, and Transwell invasion assays. The chemo- and radio-sensitizing effects of catechol on Panc-1 cells were evaluated via MTT assay and flow cytometry. Western blotting was conducted to analyze the expression of proteins involved in several mechanisms induced by catechol in Panc-1 cells, including growth inhibition, apoptosis, suppression of epithelial-mesenchymal transition (EMT), and chemo- and radio-sensitizing activities. The results indicated that catechol inhibited proliferation, promoted apoptosis, and suppressed cell migration, invasion, and EMT in Panc-1 cells in a dose-dependent manner. Catechol treatment also induced the phosphorylation of AMP-activated protein kinase (AMPK) with a concomitant reduction in the expression of Hippo signaling pathway components, including Yes-associated protein, cysteine-rich angiogenic inducer 61, and connective tissue growth factor. In addition, catechol enhanced the chemosensitivity of Panc-1 cells to gemcitabine, a commonly used chemotherapy in pancreatic cancer treatment. A combination of catechol and radiation enhanced apoptosis and increased the expression of two radiation-induced DNA damage markers, p-ATM and p-Chk2. Collectively, the present results demonstrated that catechol, a naturally occurring compound, could suppress the proliferation of pancreatic cancer cells, reduce the expression of EMT-related proteins, and enhance the chemo- and radio-sensitivity of Panc-1 cells by targeting AMPK/Hippo signaling.