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

Moon,Jeong Yong; Ediriweera,Meran Keshawa; Ryu,Ji Yeon; Kim,Hee Young; Cho,Somi Kim

doi:10.3892/or.2021.7924

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

Authors:
- Jeong Yong Moon
- Meran Keshawa Ediriweera
- Ji Yeon Ryu
- Hee Young Kim
- Somi Kim Cho
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Affiliations: Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju Special Self‑Governing Province 63243, Republic of Korea, School of Biomaterials Science and Technology, College of Applied Life Sciences, Jeju National University, Jeju Special Self‑Governing Province 63243, Republic of Korea, Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju Special Self‑Governing Province 63243, Republic of Korea
Published online on: January 5, 2021 https://doi.org/10.3892/or.2021.7924
Pages: 1133-1141
Copyright: © Moon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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