phytosterols and Leukemia--Promyelocytic--Acute

Six new cholestane glycosides (1, 5, 6, 10, 12, and 13) and two new sterols (9 and 11), along with five known compounds (2-4, 7, and 8), were isolated from the underground parts of Chamaelirium luteum (Liliaceae). The structures of these new compounds were determined by spectroscopic analysis and the results of hydrolytic cleavage. The isolated compounds and aglycones were evaluated for their cytotoxic activity against HL-60 human leukemia cells. Compounds 6a, 10a, 12a, 13, and 13a were cytotoxic to HL-60 cells, with IC50 values of 12.8, 9.8, 15.3, 6.2, and 10.2 µM, respectively.

Topics: Antineoplastic Agents; Cell Survival; Cholestanes; Drug Screening Assays, Antitumor; Glycosides; HL-60 Cells; Humans; Hydrolysis; Inhibitory Concentration 50; Leukemia, Promyelocytic, Acute; Liliaceae; Magnetic Resonance Spectroscopy; Molecular Structure; Phytosterols; Phytotherapy; Plant Extracts; Plant Roots; Plants, Medicinal

The inducer of differentiation of human promyelocytic leukemia HL-60 cells is commonly accepted to have potential therapeutic importance. Verticinone, one of the major isosteroidal alkaloids from the bulbus of Fritillaria ussuriensis, was found to inhibit the growth of HL-60 cells by inducing these cells to differentiate toward granulocytes. Importantly, the combination of verticinone with all-trans retinoic acid (ATRA), a well-known inducer of HL-60 cells into granulocytic lineages, was more effective than either alone, suggesting its therapeutic use in minimizing the effective dose of ATRA.

Topics: Alkaloids; Cell Differentiation; Cevanes; Fritillaria; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; Phytosterols; Plant Extracts; Plant Structures