15-deoxyprostaglandin-j2 has been researched along with Leukemia* in 2 studies
2 other study(ies) available for 15-deoxyprostaglandin-j2 and Leukemia
| Article | Year |
|---|---|
Activation of PPARγ by endogenous prostaglandin J
Supplementation with nontoxic doses of micronutrient selenium has been shown to alleviate chronic myelogenous leukemia (CML) via the elimination of leukemia stem cells (LSCs) in mice. This treatment provides a new and novel method for eliminating the LSCs that are otherwise not targeted by existing therapies. The antileukemic effect of selenium was dependent on the production of endogenous cyclopentenone prostaglandins (CyPGs), Δ-12 prostaglandin J Topics: Animals; Antineoplastic Agents; Dietary Supplements; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mice; PPAR gamma; Prostaglandin D2; Selenium | 2017 |
15d-PGJ2 induces apoptosis by reactive oxygen species-mediated inactivation of Akt in leukemia and colorectal cancer cells and shows in vivo antitumor activity.
Recent studies have shown that 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)), a natural ligand for peroxisome proliferator-activated receptor-gamma (PPARgamma), inhibits cell proliferation and induces apoptosis. The specific molecular mechanisms underlying this effect remain to be elucidated. We examined whether 15d-PGJ(2) has antitumor activity in vitro and in vivo, and investigated the underlying mechanism.. We examined 15d-PGJ(2)-induced apoptosis in human leukemia cells in the context of mitochondrial injury, oxidative damage, and signaling pathway disturbances. In addition, we investigated the antitumor effect of 15d-PGJ(2) in a mouse CT-26 s.c. tumor model and HL-60 leukemia xenograft model.. 15d-PGJ(2) induced apoptosis in leukemia and colorectal cancer cells in a dose-dependent manner and led to generation of reactive oxygen species (ROS) through mitochondria and NADPH oxidase activation, activation of JNK, and inactivation of Akt, a serine/threonine-specific protein kinase. Constitutive activation of Akt for an engineered myristoylated protein prevented 15d-PGJ(2)-mediated apoptosis but not ROS generation. Collectively, these findings suggest a hierarchical model of apoptosis induced by 15d-PGJ(2) in human leukemia cells: oxidative injury represents a primary event resulting in Akt inactivation, which in turn leads to mitochondrial injury and apoptosis. Moreover, 15d-PGJ(2) markedly reduced growth of mouse CT-26 s.c. tumors and HL-60 xenograft tumors and down-regulated p-Akt and Akt expression in vivo.. These results suggest that Akt inactivation through ROS production may contribute to 15d-PGJ(2)-induced apoptosis in leukemia and colorectal cancer cell lines and that 15d-PGJ(2) may have therapeutic relevance in the treatment of human leukemia and colorectal cancer. Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Colorectal Neoplasms; Humans; JNK Mitogen-Activated Protein Kinases; Leukemia; Membrane Potential, Mitochondrial; Mice; Mice, Nude; Mitochondria; NADPH Oxidases; PPAR gamma; Prostaglandin D2; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Xenograft Model Antitumor Assays | 2009 |