title: β-lactam Structured, 4-(4-(Methylsulfonyl)phenyl)-1-pentyl-3-phenoxyazetidin-2-one: Selectively Targets Cancerous B Lymphocyte Mitochondria.
abstract: BACKGROUND
  β lactam-structured Cox-2 inhibitors, possesses anti-proliferative and anti-inflammatory effects.
  
  
  OBJECTIVE
  In this research, the actions of a synthetic β lactam-structured Cox-2 inhibitor with 4-(4- (Methylsulfonyl) phenyl)-1-pentyl-3-phenoxyazetidin-2-one on cellular viability of cancerous lymphoblast obtained from patients with acute lymphocytic leukemia (ALL) and normal lymphocytes obtained from healthy donors were compared.
  
  
  METHODS
  % the cell viability of cancerouslymphoblasts and normal lymphocytes treated with β lactam derivatives were assayed with MTT test. Early apoptosis and necrosis were detected by double staining of annexin V/ propidium iodide and activity of caspase 3 as the final mediator in apoptotic mode of cell death was evaluated by colorimetric assay.
  
  
  RESULTS
  Our results showed that β lactam derivatives inhibited the proliferation of cancerous lymphoblast but not normal lymphocytes in a concentration-dependent mode by inducing apoptosis. Treatment with β lactam derivatives resulted in a rapid loss of mitochondrial trans-membrane potential and induction of reactive oxygen species (ROS) formation, and cytochrome c release in cytosol of mitochondria resulted in activation of procaspase-9 and formation of active apoptosome.
  
  
  CONCLUSIONS
  These findings suggest that 4-(4-(Methylsulfonyl)phenyl)-1-pentyl-3-phenoxyazetidin-2-one as a β lactam could induce ROS-mediated death signaling throughmitochondrial pathway that results in apoptosis in only cancerous lymphoblast cells. The stimulationof apoptosis by β lactams may provide a pivotal mechanismfor their anticancer effect in acute lymphocytic leukemia cells.
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran. Iran.
authors.forename: Nahal
authors.initials: N
authors.lastname: Pirahmadi
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran. Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Zarghi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil. Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salimi
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran. Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Arefi
authors.affiliation: Toxicology and Pharmacology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran. Iran.
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001385:Azetines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D045304:Cytochromes c / Q000037:antagonists & inhibitors / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000623217:4-(4-(methylsulfonyl)phenyl)-1-pentyl-3-phenoxyazetidin-2-one; D000970:Antineoplastic Agents; D001385:Azetines; D017382:Reactive Oxygen Species; D047090:beta-Lactams; D045304:Cytochromes c
keywords: Mitochondria; acute lymphocytic leukemia.; apoptosis; cox-2 inhibitors; β lactam