title: Ultra-violet irradiation induces apoptosis via mitochondrial pathway in pancreatic cancer cells.
abstract: Pancreatic cancer is a highly lethal disease and gemcitabine is considered to be the standard of care for the treatment of advanced pancreatic cancer. However, the outcome of the patients treated with gemcitabine is still unstatisfactory and further development of new treatments is required. We recently found that short wavelength ultra-violet (UV-C) suppresses cell proliferation with downregulation of epidermal growth factor receptor (EGFR) in human pancreatic cancer cells, but not in normal pancreatic epithelial (PE) cells. In this study, we investigated the effect of UV-C on apoptosis in several cell lines derived from the pancreas. UV-C induced poly(ADP-ribose) polymerase (PARP) cleavage, which is a marker of cells undergoing apoptosis, in Panc1, MiaPaca2, KP3 and BxPC3 pancreatic cancer cells, but not in PE cells. We also observed similar effects in Hoechst 33258 staining, which shows DNA fragmentation. While p53, a tumor suppressor protein, plays a critical role in UV-C-induced cell damage, we did not observe the correlation between the sensitivity to UV-C and p53 status. Thapsigargin, an agent that promotes endoplasmic reticulum (ER) stress by depletion of lumenal calcium stores, as well as cis-diamineplatinum (II) dichloride, a classical anti-cancer drug that causes DNA damage, induced PARP cleavage even in PE cells. Moreover, UV-C-induced apoptosis in Panc1 and KP3 cells was associated with the release of cytochrome c, indicating that it was mediated via mitochondrial pathway. Taken together, UV-C has a potent anti-cancer effect on pancreatic cancer cells without adverse effect on normal cells and it could be useful for the treatment of human pancreatic cancers.
authors: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors: Takahiro
authors: T
authors: Yamauchi
authors: Seiji
authors: S
authors: Adachi
authors: Ichiro
authors: I
authors: Yasuda
authors: Masanori
authors: M
authors: Nakashima
authors: Junji
authors: J
authors: Kawaguchi
authors: Takashi
authors: T
authors: Yoshioka
authors: Yoshinobu
authors: Y
authors: Hirose
authors: Osamu
authors: O
authors: Kozawa
authors: Hisataka
authors: H
authors: Moriwaki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects*; D010179:Pancreas / Q000378:metabolism / Q000528:radiation effects; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D019284:Thapsigargin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016159:Tumor Suppressor Protein p53; D019284:Thapsigargin; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin