Study of molecular mechanism of tanshinone II A inducing differentiation in acute promyelocytic leukemia NB4 cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate molecular mechanism of tanshinone II A inducing differentiation and apoptosis in acute promyelocytic leukemia NB4 cells.</p><p><b>METHOD</b>NB4 cells were cultured in vitro and treated with tanshinone II A and observed cellular morphology, cell category and the cellular proliferation. DNA microarray technique was used to analyze the gene expression profiles of NB4 cells induced by tanshinone II A.</p><p><b>RESULT</b>92.8% of NB4 cells treated with 0.5 mg x L(-1) tanshinone II A were induced into mature neutrophils, in which myetocytes and melamyetocytes were 27.0%, banded and segmented neutrophits 68.2%. Cell growth were inhibited. cDNA microarray showed the enormously expressed 183 genes including 23 differentiation associated genes, and other interrelated genes.</p><p><b>CONCLUSION</b>Tanshinone II A inducing differentiation in NB4 cells may be via regulation of many kinds of genes, especially differentiation associated genes expression. This partially explained the molecular mechanism of tanshinone II A inducing differentiation.</p>

Alteration of activities of telomerase in tanshinone IIA inducing apoptosis of the leukemia cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of tanshinone IIA on HL-60 and K562 cells apoptosis, and to assay the inhibition of the telomerase activities in the leukemia cell apoptosis induced by Tanshinone.</p><p><b>METHOD</b>Using the techniques of cell culture in vitro, flow cytometry and PCR-TRAP observed the telomerase activities and apoptosis of HL-60 and K562 cells which treated by Tan IIA.</p><p><b>RESULT</b>0.5 microg x mL(-1) Tan IIA could obviously inhibit HL-60 and K562 cell lines growth (P < 0.05), down-regulate c-myc, bcl-2 gene and up-regulate c-fos and p53 gene expression as well as induce leukemia cell apoptosis, the apoptotic rates of HL-60 and K562 cells were 11.8% and 21.8% respectively. The telomerase activities significant decreased, the inhibiting rates in HL60 and K562 cells were 30.8% and 50.8% respectively.</p><p><b>CONCLUSION</b>Tan IIA could significantly inhibit the proliferation and telomerase activities of HL-60 and K562 cells and induce the leukemia cell apoptosis.</p>

Identification of the metabolites of penehyclidine hydrochloride raceme in rats by LC-MS/MS and ion cluster / 药学学报

<p><b>AIM</b>To study the metabolites of penehyclidine hydrochloride (PH) raceme, a new anticholinerigic drug invented by the Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences.</p><p><b>METHODS</b>Three healthy rat urine samples were collected within 24 h after a single i.m. dose of PH raceme and PH-d5 [(5 + 5) mg.kg-1] simultaneously. The eight metabolites of PH raceme were identified by the methods of LC-MS/MS, GC-MS, FAB-MS and the stable isotope ion cluster. Mass spectrometry was operated in the positive mode for the method of LC-MS/MS.</p><p><b>RESULTS</b>M1 and M1* were identified as the oxygenated products of PH in the cyclopentyl group; M2 and M2* were as the hydroxylated products of PH in the cyclopentyl group; M3 and M3* were as the oxygented and hydroxylated products of PH at the meta-position of cyclopentyl group; M4 and M4* were identified as the dihydroxylated metabolites of PH, the hydroxylated position were at the cyclopentyl group and quiniuclidinol ring of PH. Among them, M1 and M1*, M2 and M2*, M3 and M3*, M4 and M4* were the isomers of each other.</p><p><b>CONCLUSION</b>These characteristics can be used for future structure elucidation in studies of the metabolites of PH optical isomers. The structure data of PH metabolites provide important information for the clinical use and for developing better anticholinerigic drug.</p>