Comparison of In Vitro Antileukemic Activity of 4-Hydroperoxyifosfamide and 4-Hydroperoxycyclophosphamide.

Abstract:

BACKGROUND/AIM:The oxazaphosphorines, ifosfamide and cyclophosphamide, represent a class of alkylating agents. The aim of the present in vitro study was to compare antileukemic activity of 4-hydroperoxyifosfamide (4-OOH-IF) and 4-hydroperoxycyclophosphamide (4-OOH-CP). MATERIALS AND METHODS:The experiments were performed on MOLT-4 and ML-1 cells. The research was conducted using flow cytometry fluorescein diacetate/propidium iodide (PI), fluorescein-conjugated annexin V/PI, CaspGLOW Red Active Caspase-8 and -9, CellEvent™ Caspase-3/7 Green assays, and tetramethylrhodamine ethyl ester test. RESULTS:4-OOH-IF and 4-OOH-CP distinctly reduced cell viability and triggered apoptosis and necrosis, causing changes in intracellular esterase activity, plasma membrane structure and integrity, caspase activation, and mitochondrial membrane potential. The oxazaphosphorines were responsible for the different antileukemic activities. 4-Hydroperoxyifosfamide appeared to be less cytotoxic against the leukemia cells than 4-hydroperoxycyclophosphamide. MOLT-4 cells were more sensitive to the action of the oxazaphosphorines than ML-1 cells. CONCLUSION:The findings provide a new insight on the mechanisms of cytotoxic action of 4-OOH-IF and 4-OOH-CP on the human acute lymphoblastic and myeloblastic leukemia cells.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Opydo-Chanek M,Śladowska K,Blicharski K,Mikeš J,Fedoročko P,Niemeyer U,Mazur L

doi

10.21873/anticanres.12088

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

6355-6361

issue

11

eissn

0250-7005

issn

1791-7530

pii

37/11/6355

journal_volume

37

pub_type

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