-
[show abstract]
[hide abstract]
ABSTRACT: Ursolic acid (UA), a pentacyclic triterpenoid derived from a variety of medicinal plants, exhibits potent anticancer activity against many types of cancer cells. However, the anticancer mechanism of UA is not clearly understood. Suppression of phosphatase and a tensin homolog deleted on chromosome 10 (PTEN) gene expression leading to activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway has been observed in many cancers including leukemia, making the PTEN gene and PI3K/Akt pathway a central target for cancer therapy. Here, we demonstrated that UA was able to inhibit growth, induce apoptosis in a human chronic myelogenous leukemia cell line (K562 cells) via upregulation of PTEN gene expression, inhibit Akt kinase activity, change mitochondrial transmembrane potential and reduce the release of cytochrome c and the activity of caspases. These results suggest that UA may elicit its strong antitumor effects via upregulation of the PTEN gene and inhibition of the PI3K/Akt pathway.
Archives of Pharmacal Research 03/2012; 35(3):543-8. · 1.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was purposed to investigate the effects of high-dose methotrexate (HD-MTX)-CF + VDT protocol on pediatric acute lymphoblastic leukemia (ALL) by means of retrospective analysis. MTX plasma concentration was dynamically detected and evaluated so as to avoid or reduce the side effects of HD-MTX, and adjust the time and dosage of calcium folinate (CF) or carry out the plasma exchange as occasion requires. Totally 180 cases of ALL were enrolled in this study, and received 380 administration of HD-MTX-CF + VDT protocol, including 122 patients with induction therapy as well as 58 cases during maintenance therapy, among which 68 cases were defined as low risk, 80 cases as middle risk and 32 cases as high risk. 2.0 g/m(2) MTX, 3.0 g/m(2) MTX, and 5.0 g/m(2) MTX were individually used according to low risk, middle risk or T immunohistochemical expression. The results indicated that 36.3% cases showed the side-effects of HD-MTX including mucocutaneous lesions, gastrointestinal reaction, hepatic dysfunction, renal damage, fever, myelosuppression, cardiotoxicity, infection and allergic response. All of these side effects were reversible through treatment. The elimination delay of MTX occurred in 110 cases, out of which 3 cases got MTX concentration > 10 µmol/L at 24 hours, 50 cases > 1.0 µmol/L at 44 hours, the remaining 57 cases > 0.1 µmol/L at 68 hours. CF dosage was adjusted according to the concentration of MTX until it was less than 0.1 µmol/L. 1 case had renal interstitial inflammation and acute renal failure, but finally he was cured. No patients received plasma exchange or died. It is concluded that the extramedullary leukemia control protocol, in which MTX is main drug, is effective therapy for obtaining long-term remission and event-free survival rate in ALL patients, but the side effects and risks increase along with the increase of MTX dose. The metabolic level of HD-MTX has found to be obvious individual, so the dynamic monitoring of MTX concentration in plasma and administration of proper dosage of CF are important factors for HD-MTX protocol application in ALL patients.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 07/2011; 19(4):949-52.
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to investigate the apoptosis effect of Jurkat cells induced by ursolic acid (UA) and its molecular mechanism so as to provide the theoretical basis for treatment of hematological malignancies by using UA. The cytotoxic effect of different concentration UA on Jurkat cells and inhibitory effect of caspase-9 inhibitor on cytotoxicity of UA were assayed by using WST-8 method; the Jurkat cells treated with 20 or 40 micromol/L UA for 2 or 4 hours were collected and were stained by Annexin/PI, then the apoptosis rate of Jurkat cells was detected by flow cytometry; the Jurkat cells in logarithmic growth phase were collected after treatment with different concentrations of UA for different times, the cell protein was extracted, then the activation of caspase-9, -3 and cytochrome C as well as phosphorylation level of Akt were determined by Western blot. The results indicated that the cytotoxic effect of UA on Jurkat cells was significant. UA induced apoptosis of Jurkat cells. Caspase-9, caspase-3 and cytochrome C were activated, and the phosphorylation of Akt was inhibited in the Jurkat cell apoptosis process induced by UA. It is concluded that the UA shows significant cytotoxic effect on Jurkat cells, UA can induce apoptosis of Jurkat cells through the mitochondria pathway. The mechanism may be associated with the inhibition of Akt phosphorylation.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2010; 18(1):61-6.
