title: Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation             by inducing apoptosis.
abstract: Isothiocyanates are a class of naturally occurring chemopreventive agents known to suppress proliferation of cancer cells in culture. The present study was undertaken in order to examine the effects of benzyl isothiocyanate (BITC), one of the common dietary isothiocyanates, on the radiosensitivity of human pancreatic cancer cells and to gain insights into the underlying molecular mechanism of BITC-induced radiosensitization. Two human pancreatic cancer cell lines, PANC-1 and MIAPaCa-2, were treated with BITC and irradiated with X-rays. Radiation sensitivity, apoptosis, and protein levels were determined by a clonogenic assay, fluorescence microscopic analysis with DAPI staining and Western blotting, respectively. MIAPaCa-2 cells were relatively more sensitive to BITC treatment compared with PANC-1 cells. Radiosensitization was observed in both PANC-1 and MIAPaCa-2 cells incubated with BITC at 5 to 10 µM and 2.5 to 5 µM for 24 h, respectively. The combination treatments with BITC and X-rays also revealed an increased percentage of apoptotic cells. In addition, treatment with BITC and X-rays resulted in a decrease in the protein levels of the X-linked inhibitor of apoptosis (XIAP), inhibitor of apoptosis (IAP) family protein, and in a marked increase in the apoptosis protease activating factor-1 (Apaf-1), essential for activation of caspase-9 in stress-induced apoptosis. BITC may be a useful radiosensitizer for radiotherapy of pancreatic cancers.
authors.affiliation: Department of Radiological Sciences, Center for Humanity and                     Sciences, Ibaraki Prefectural University of Health Sciences, Ami, Inashiki-gun,                     Ibaraki 300-0394, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Ohara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kimura
authors.forename: Aya
authors.initials: A
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okayasu
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kubota
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D008856:Microscopy, Fluorescence; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D014965:X-Rays
chemical_list: C506592:APAF1 protein, human; D000970:Antineoplastic Agents; D053477:Apoptotic Protease-Activating Factor 1; D017879:Isothiocyanates; D011838:Radiation-Sensitizing Agents; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C031403:benzyl isothiocyanate; D053453:Caspase 9