Cell differentiation and apoptosis of monocytic and promyelocytic leukemia cells (U‐937 and HL‐60) by tryptanthrin, an active ingredient of Polygonum tinctorium Lour.

Abstract

Tryptanthrin, a bioactive ingredient of Polygonum tinctorium Lour., is a member of the Indigo plant family and has potent cytocidal effects on various human leukemia cells in vitro. At low concentrations, tryptanthrin enhanced the expression of cell differentiation (CD) markers in human monocytic (U-937) and promyelocytic (HL-60) leukemia cells indicative of differentiation to monocytes/macrophages. Furthermore, nitroblue tetrazolium (NBT) reductive and alpha-naphthyl butyrate esterase (NBE) activities were markedly increased after treatment. Tryptanthrin was more potent than dimethyl sulfoxide (DMSO) at inducing U-937 cell differentiation into monocytes/macrophages. After treatment with higher concentrations of tryptanthrin for 24 h, cytoplasmic vacuolation and destruction of mitochondria were observed. The leukemia cells died via apoptosis 48 h after treatment. Cytoplasmic vacuolation and apoptotic changes correlated with the dysfunction of mitochondria. Electron microscopic observations revealed marked swelling and destruction of mitochondria after exposure of the leukemia cells to tryptanthrin. Exposure to tryptanthrin enhanced Fas-induced apoptosis and increased caspase-3 activity before induction of apoptosis. These results show that low concentrations of tryptanthrin can induce differentiation of leukemia cells but higher concentrations will kill leukemia cells through apoptosis, possibly through a caspase-3/Fas antigen pathway.

Cytotoxicity and reversal of multidrug resistance by tryptanthrin-derived indoloquinazolines

“…Tryptanthrin with chemical name indolo [2,1-b] quinazolin-6,12-dione was reported to carry anti-microbial activity against a variety of microorganisms including bacteria, yeasts, dermatophytes and phytopathogens [10,11] . Recently, tryptanthrin has been paid much attention as an aryl hydrocarbon receptor agonist [12] , anti-inflammatory agent [13] , inducer of caspase-3/Fas mediated apoptosis [14] , cytostatic agent [15] and drug resistance reversal agent [16] . In this study, a series of tryptanthrin derivatives were synthesized and designated as compounds 1-7.…”

Modulatory Effects and Action Mechanisms of Tryptanthrin on Murine Myeloid Leukemia Cells

“…Tryptanthrin is a phytochemical found in the medicinal indigo plants such as Polygonum tinctorium and Isatis tinctoria. It was found to possess a wide spectrum of biological and pharmacological activities, including anti-microbial (7-9), immunomodulatory (11-13), antiinflammatory (13-15) and anti-tumor (16)(17)(18)(19) activities. A previous report has shown that tryptanthrin is able to induce both apoptosis and differentiation in the human leukemia HL-60 cells and U-937 cells in vitro (16), however, the underlying action mechanisms remain unclear.…”

“…It was found to possess a wide spectrum of biological and pharmacological activities, including anti-microbial (7-9), immunomodulatory (11-13), antiinflammatory (13-15) and anti-tumor (16)(17)(18)(19) activities. A previous report has shown that tryptanthrin is able to induce both apoptosis and differentiation in the human leukemia HL-60 cells and U-937 cells in vitro (16), however, the underlying action mechanisms remain unclear. In this study, the anti-proliferative and differentiation-inducing activities of tryptanthrin on the murine myelomonocytic leukemia WEHI-3B JCS cells were investigated and the possible anti-tumor mechanisms were elucidated.…”

“…Reaction mixture containing 40 units of RN ASE OUT TM recombinant ribonuclease inhibitor, 1 M-MLV first strand buffer, 0.5 mM of each dNTP, 10 mM DTT, 0.1g oligo (dT) [12][13][14][15][16][17][18] and 200 units of M-MLV reverse transcriptase was prepared, and 2 g RNA sample was added into 20 l reaction mixture. A negative control using DEPCtreated water instead of RNA sample was used to check if there was any contamination.…”

“…It was first isolated from Strobilanthes cusia as an anti-fungal agent against dermatophytes (7). Tryptanthrin is a weakly basic alkaloid and has been reported to have various biological and pharmacological activities, such as inhibitory activities against a variety of microorganisms and parasites (7)(8)(9)(10), immunomodulatory (11)(12)(13) and anti-inflammatory activities (13)(14)(15), and anti-tumor activity towards human leukemia and breast cancer cell lines in vitro (16)(17)(18). Moreover, the crude ethyl acetate extract and tryptanthrin extracted from the indigo plant Polygonum tinctorium have cancer chemopreventive activity by prevention of azoxymethane-induced intestinal tumor formation in F344 rats (19).…”