Pisosterol induces monocytic differentiation in HL-60 cells.
The aim of this study was to determine whether the antiproliferative effects observed for pisosterol, a cytotoxic triterpene isolated from Pisolithus tinctorius, are related to cell differentiation induction using HL-60 cell line as a model. Also, the effects of pisosterol on normal human cells were examined in peripheral blood mononuclear cells (PBMC). The effects on cell viability and morphological changes were the first indications showing that pisosterol induces HL-60 differentiation. The demonstration of blue tetrazolium reduction in HL-60 cells exposed to pisosterol demonstrated differentiation in a dose- and time-dependent manner, reaching a maximum effect after 72 h incubation at 5 microg/mL. Assays for alpha-naphthyl acetate esterase activity indicated that pisosterol triggers differentiation towards a monocytic cell-like pathway. The antiproliferative effect of pisosterol was determined by inhibition of DNA synthesis based on BrdU incorporation into HL-60 proliferating cells. It appears that pisosterol-treated cells, despite displaying a differentiated phenotype, continued to proliferate at all doses tested after 72 h, with a slightly decrease at 5 microg/mL. Apoptosis was observed in pisosterol-treated cells in a dose-dependent way. Nevertheless, after the same period of incubation, no cytotoxicity was detected in PBMC in the presence of pisosterol even at 25 microg/mL, providing some evidence that pisosterol may be selective for tumor cells. The mechanisms underlying the effect of pisosterol in leukemia cells indicates the induction of a monocytic cell-like differentiation, suggesting that this compound could be used in the development of new pharmacological tools with potential therapeutic value in the management of leukemia with fewer side effects.
Montenegro
Raquel Carvalho
RC
Laboratório de Oncologia Experimental, Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box 3157, 60430-270 Fortaleza, Ceará, Brazil.
de Vasconcellos
Marne Carvalho
MC
Silva Bezerra
Franciglauber
F
Andrade-Neto
Manoel
M
Pessoa
Cláudia
C
de Moraes
Manoel Odorico
MO
Costa-Lotufo
Letícia Veras
LV
D000963:Antimetabolites; D001487:Basidiomycota / Q000737:chemistry*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D018922:HL-60 Cells; D006801:Humans; D009000:Monocytes / Q000187:drug effects*; D009283:Naphthol AS D Esterase / Q000378:metabolism; D009580:Nitroblue Tetrazolium; D013729:Terpenes / Q000494:pharmacology*; D014343:Trypan Blue
D000963:Antimetabolites; D005456:Fluorescent Dyes; D013729:Terpenes; C522992:pisosterol; D009580:Nitroblue Tetrazolium; D004247:DNA; D009283:Naphthol AS D Esterase; D001973:Bromodeoxyuridine; D014343:Trypan Blue