title: Ursolic acid-induced apoptosis in K562 cells involving upregulation of PTEN gene expression and inactivation of the PI3K/Akt pathway.
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.
authors.affiliation: Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Zuo-fei
authors.initials: ZF
authors.lastname: Chi
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Zhuo-gang
authors.initials: ZG
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020169:Caspases; D045304:Cytochromes c; D051059:PTEN Phosphohydrolase; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D014315:Triterpenes; D000097245:Ursolic Acid; C494929:PTEN protein, human