Title:β-lactam Structured, 4-(4-(Methylsulfonyl)phenyl)-1-pentyl-3-phenoxyazetidin-2-one: Selectively Targets Cancerous B Lymphocyte Mitochondria
Volume: 17
Issue: 9
Author(s): Nahal Pirahmadi, Afshin Zarghi, Ahmad Salimi, Hadi Arefi and Jalal Pourahmad*
Affiliation:
- Toxicology and Pharmacology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran,Iran
Keywords:
Mitochondria, cox-2 inhibitors, β lactam, apoptosis, acute lymphocytic leukemia.
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.
Conclusion: 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.
