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 GSK3β 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)
Animals , Humans , Mice , Apoptosis , Brucea/chemistry , Glycogen Synthase Kinase 3 , Jurkat Cells , Phosphatidylinositol 3-Kinases/genetics , Plant Oils/pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Proto-Oncogene Proteins c-akt/genetics , Seeds/chemistry , Signal TransductionABSTRACT
Recently, the incidence and mortality of cancer has raised. More and more cytotoxic drugs and molecular targeted medicines have been used in clinic. However, most drugs just display a short-term anti-tumor effect. If patients received treatment for a long time, it would arise resistance to chemotherapy frequently. One of its important reasons is the accumulation of drug induced cancer cells. Thus, this paper emphasizes on biological character of drug induced cells, including cell biological phenotype, the change of gene and protein, variation of metabolism, dynamic change of signal transduction pathway and so on. Meanwhile, according to the characteristics of drug induced cells, we propose some strategies to inhibit drug induced cells, which would provide the foundation of clinical therapy and novel anti-tumor drug research and development.
ABSTRACT
<p><b>OBJECTIVE</b>To determine the effect of three Jianpi Buqi recipes on intestinal microflora of Pi-qi-deficiency rat with molecular biology methods and attempt to clarify the mechanisms of therapy.</p><p><b>METHOD</b>Rat model of Pi-qi-deficiency was induced by exercise fatigue simultaneously diet incontinence and then administrated with the decoctions of Si-jun-zi-tang (including crude drug) (10.8, 3.6, 1.2 g x kg(-1)), Li-zhong-tang (16.2, 5.4, 1.8 g x kg(-1)) and Buzhong Yiqi-tang (14.4, 4.8, 1.6 g x kg(-1)) recipes which were in common use of clinic of traditional Chinese medicine (TCM). With application of ERIC-PCR (enterobacterial repetitive intergenic consensus-PCR) fingerprint analysis, the efficacy on Pi-qi-deficiency and perturbation of intestinal mircoflora of these recipes were examined and evaluated.</p><p><b>RESULT</b>Remarkable differences of ERIC-PCR profile were found between Pi-qi-deficiency state rats and normal rats. The Shannon's Index (H') was increased when treated with all doses of three Jianpibuqi recipes decoctions and Sorenson's pairwise similarity coefficient (Cs) was also increased significantly after treatment.</p><p><b>CONCLUSION</b>ERIC-PCR fingerprint can be utilized as an initial screening of changes of the composition of bacterial communities that are associated with the development of intestinal disease. It can also be used to build a better understanding of Pi-qi-deficiency and to investigate the pharmacodynamic effect of TCM on Pi-qi-deficiency. Three Jianpi Buqi recipes are demonstrated to produce pronounced recovery activities on intestinal microflora of Pi-qi-deficient rats, which may be considered one of mechanisms of their performances.</p>
Subject(s)
Animals , Female , Male , Rats , Bacteria , Genetics , Drugs, Chinese Herbal , Pharmacology , Feces , Microbiology , Intestines , Microbiology , Polymerase Chain Reaction , Rats, WistarABSTRACT
The effects of ginsenosides on the actions of morphine are summarized. It mainly focuses on the antagonistic effects of ginsenosides on morphine-induced changes of animal behaviors, neural system functions and cell signaling transduction.