β-lactam Structured, 4-(4-(Methylsulfonyl)phenyl)-1-pentyl-3-phenoxyazetidin-2-one: Selectively Targets Cancerous B Lymphocyte Mitochondria

Author(s): Nahal Pirahmadi, Afshin Zarghi, Ahmad Salimi, Hadi Arefi, Jalal Pourahmad*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 17 , Issue 9 , 2017

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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.

Keywords: Mitochondria, cox-2 inhibitors, β lactam, apoptosis, acute lymphocytic leukemia.

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Article Details

VOLUME: 17
ISSUE: 9
Year: 2017
Page: [1292 - 1301]
Pages: 10
DOI: 10.2174/1871520617666170213144113
Price: $58

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