title: Endostatin and irradiation modifies the activity of ADAM10 and neprilysin in breast cancer cells.
abstract: Angiogenesis, the formation of new blood vessels, is regarded as a key cancer cell property. Endostatin (ES) is a potential antiangiogenic agent and it may be useful when implemented in combination with other cancer therapeutic strategies. The present study investigated the in vitro effects of ES, radiotherapy (RT) or combination therapy (ES + RT) on two important proteases, a disintegrin and metalloproteinase domain‑containing protein 10 (ADAM10) and neprilysin (NEP) in 4T1 mouse breast cancer cells and the more metastatic phenotype of 4THMpc breast cancer cells. 4T1 and 4THMpc cells were treated with recombinant murine ES (4 µg/ml) alone, RT (45 Gy) alone or with ES + RT. ADAM10 enzyme activity was determined using a tumor necrosis factor‑α converting enzyme (α‑secretase) activity assay kit, and NEP enzyme activity was measured with a fluorometric assay based on the generation of free dansyl‑D‑Ala‑Gly from N-dansyl-Ala-Gly-D-nitro-Phe-Gly, the substrate of NEP. Western blotting analysis was performed to determine whether the altered enzyme activity levels of the two cell lines occurred due to changes in expression level. These data indicate that ES independently potentiates the activity of ADAM10 and NEP enzymes in 4T1 and 4THMpc breast cancer cells.
authors.affiliation: Department of Biology, Science Faculty, Akdeniz University, Antalya 07058, Turkey.
authors.forename: Esra Arslan
authors.initials: EA
authors.lastname: Aydemir
authors.affiliation: Department of Nutrition and Dietetics, Antalya School of Health, Akdeniz University, Antalya 07058, Turkey.
authors.forename: Ece
authors.initials: E
authors.lastname: Şimşek
authors.affiliation: Department of Radiation Oncology, School of Medicine, Akdeniz University, Antalya 07058, Turkey.
authors.forename: Aylin Fidan
authors.initials: AF
authors.lastname: Korcum
authors.affiliation: Department of Nutrition and Dietetics, Antalya School of Health, Akdeniz University, Antalya 07058, Turkey.
authors.forename: Kayahan
authors.initials: K
authors.lastname: Fişkin
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D043169:Endostatins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism; D015260:Neprilysin / Q000378:metabolism*; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D015260:Neprilysin; D000072197:ADAM10 Protein