Epicatechin stimulates mitochondrial activity and selectively sensitizes cancer cells to radiation

• Published in: PloS one 2014-02, Vol.9 (2), p.e88322-e88322
• Main Authors: Elbaz, Hosam A, Lee, Icksoo, Antwih, Deborah A, Liu, Jenney, Hüttemann, Maik, Zielske, Steven P
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Biology; Brain cancer; Cancer; Cancer cells; Cancer therapies; Caspase 3 - metabolism; Catechin - pharmacology; Cell culture; Cell cycle; Cell Line, Tumor; Cell Respiration - drug effects; Cell Respiration - radiation effects; Cell survival; Checkpoint Kinase 2 - metabolism; Chemotherapy; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cytochrome; Deoxyribonucleic acid; DNA; Drugs; Electron transport; Electron Transport - drug effects; Electron Transport - radiation effects; Epicatechin; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fibroblasts - radiation effects; Flavonoids; Fruits; Glioblastoma; Humans; Ionizing radiation; Kinases; Medical research; Medicine; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - radiation effects; Oncology; Oxygen; Oxygen consumption; Pancreatic cancer; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - pathology; Phosphorylation; Phosphorylation - drug effects; Phosphorylation - radiation effects; Phosphothreonine - metabolism; Polyphenols; Proteins; Radiation; Radiation therapy; Radiation tolerance; Radiation Tolerance - drug effects; Radiation Tolerance - radiation effects; Radiation, Ionizing; Radiation-Sensitizing Agents - pharmacology; Radiotherapy; Respiration; Senescence; Solid tumors; Tumors; Vegetables
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088322

Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (-)-epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (-)-epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and Western blot analyses. (-)-Epicatechin stimulated mitochondrial respiration and oxygen consumption in Panc-1 cells. Human normal fibroblasts were not affected. (-)-Epicatechin sensitized Panc-1, U87, and MIA PaCa-2 cells with an average radiation enhancement factor (REF) of 1.7, 1.5, and 1.2, respectively. (-)-Epicatechin did not sensitize normal fibroblast cells to ionizing radiation with a REF of 0.9, suggesting cancer cell selectivity. (-)-Epicatechin enhanced Chk2 phosphorylation and p21 induction when combined with radiation in cancer, but not normal, cells. Taken together, (-)-epicatechin radiosensitized cancer cells, but not normal cells, and may be a promising candidate for pancreatic cancer treatment when combined with radiation.