title: Epicatechin stimulates mitochondrial activity and selectively sensitizes cancer cells to radiation.
abstract: 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.
authors: Department of Radiation Oncology, Wayne State University, Detroit, Michigan, United States of America ; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, United States of America ; Wayne State University and Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors: Hosam A
authors: HA
authors: Elbaz
authors: College of Medicine, Dankook University, Cheonan-si, Chungcheongnam-do, Republic of Korea.
authors: Icksoo
authors: I
authors: Lee
authors: Department of Radiation Oncology, Wayne State University, Detroit, Michigan, United States of America ; Wayne State University and Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors: Deborah A
authors: DA
authors: Antwih
authors: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, United States of America ; Wayne State University and Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors: Jenney
authors: J
authors: Liu
authors: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, United States of America ; Cardiovascular Research Institute, Wayne State University, Detroit, Michigan, United States of America ; Wayne State University and Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors: Maik
authors: M
authors: Hüttemann
authors: Department of Radiation Oncology, Wayne State University, Detroit, Michigan, United States of America ; Wayne State University and Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors: Steven P
authors: SP
authors: Zielske
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects / Q000528:radiation effects; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D010769:Phosphothreonine / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D011838:Radiation-Sensitizing Agents; D010769:Phosphothreonine; D002392:Catechin; D064447:Checkpoint Kinase 2; D053148:Caspase 3