Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines

Faten Merhi¹, Jacques Auger², Francine Rendu¹, Brigitte Bauvois¹

¹UMR 7131 UPMC Paris Universitas/CNRS, Groupe Hospitalier Broussais-HEGP, Paris, France; ²University F. Rabelais, IRBI, UPRESA CNRS 6035, Tours, France

Abstract: Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All₂TS), dipropyl TS (Pr₂TS) and dimethyl TS (Me₂TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr₂TS and Me₂TS, but not All₂TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-α protein, without altering mRNA levels. By establishing for the first time that Pr₂TS and Me₂TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.

Keywords: acute myeloid leukemia, thiosulfinate, proliferation, differentiation, matrix metalloproteinase-9