ABSTRACT
Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3ß was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.
Subject(s)
Apoptosis , Brucea , Plant Oils/pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Animals , Brucea/chemistry , Glycogen Synthase Kinase 3 , Humans , Jurkat Cells , Mice , Phosphatidylinositol 3-Kinases/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Proto-Oncogene Proteins c-akt/genetics , Seeds/chemistry , Signal TransductionABSTRACT
A new friedelane-type triterpene (1), along with seven known triterpenoids, was isolated from the stems and leaves of Calophyllum inophyllum Linn. Their structures were established as 3beta, 23-epoxy-friedelan-28-oic acid (1), friedelin (2), epifriedelanol (3), canophyllal (4), canophyllol (5), canophyllic acid (6), 3-oxo-friedelan-28-oic acid (7), and oleanolic acid (8) by spectroscopic methods (NMR, EI-MS). The growth inhibitory effects of these triterpenoids on human leukemia HL-60 cells were determined.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Calophyllum/chemistry , Triterpenes/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Molecular Structure , Triterpenes/chemistryABSTRACT
A series of novel 2-phenylaminopyrimidine (PAP) derivatives structurally related to STI-571 were designed and synthesized. The abilities of these compounds to inhibit proliferation were tested in human chronic myeloid leukemia K562 cells. (E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide(12d) was the most effective cell growth inhibitor and was 3-fold more potent than STI-571.
Subject(s)
Acrylamides/chemistry , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Drug Design , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Piperazines/chemistry , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemistry , Acrylamides/chemical synthesis , Acrylamides/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzamides , Cell Line, Tumor , Fusion Proteins, bcr-abl/antagonists & inhibitors , Fusion Proteins, bcr-abl/metabolism , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Piperazines/chemical synthesis , Piperazines/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Pyrimidines/chemical synthesis , Pyrimidines/pharmacologyABSTRACT
Three new sterols, 3beta,16alpha-dihydroxy-5alpha,17beta-cholestan-21-carboxylic acid (1), 3beta-acetoxy-16alpha-hydroxy-5alpha,17beta-cholestan-21-carboxylic acid (2) and 3beta-(3-hydroxybutyroxy)-16alpha-hydroxy-5alpha,17beta-cholestan-21-carboxylic acid (3) were isolated from Selaginella tamariscina (Beauv.) Spring (Selaginellaceae). Their structures were elucidated based on NMR analyses. The growth inhibitory effects and differentiation induction abilities of compounds 1 - 3 were determined in human leukemia HL-60 cells. Compound 1 was more effective than compounds 2 and 3 in inhibiting cell growth, but compound 3 was more effective than compounds 1 and 2 in enhancing induction of all- trans-retinoic acid differentiation.
