Pipoxolan HCl (5,5-diphenyl-2-(2'-piperidino-ethyl)-1,3-dioxolane-4-one hydrochloride) is a compound containing a dioxolan moiety that was reported to induce apoptosis in
cancer cells. In this study, we investigated the anti-
leukemia effects of
pipoxolan on U937
leukemia cells both in vivo and in vitro. Cell viability,
reactive oxygen species (ROS) production, mitochondrial membrane potential, apoptosis and caspases-9 and -3 activity were examined following treatment of U937
leukemia cells with 10 µM
pipoxolan by flow cytometry and
caspase-activity assay. The apoptosis-associated Bcl-2 family
proteins, Bax, Bcl-2 and Bcl-xL, were examined by Western blotting. We found that
pipoxolan inhibited U937 cell proliferation in a dose- and time-dependent manner. Morphological assessment and cell cycle analysis indicated that
pipoxolan induced the apoptosis of the U937 cells.
Pipoxolan (10 µM) increased ROS production and decreased mitochondrial membrane potential 1 h after
pipoxolan treatment. Pre-treatment of
pipoxolan-treated cells with
N-acetyl-L-cysteine (a ROS
chelator) inhibited the increase in ROS production.
After treatment with 10 µM
pipoxolan for 24 h, there was an increase in pro-apoptotic Bax and a decrease in anti-apoptotic Bcl-2 and Bcl-xL
proteins. In vivo, we found that
pipoxolan significantly suppressed
tumor growth in BALB/
cnu-/nu- mice inoculated with U937 cells. Taken together, the data from our studies indicate that
pipoxolan possesses potent anti-
leukemia activity and is a potential novel alternative
cancer therapeutic agent for human
leukemia.