title: PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma.
abstract: Aberrant activation of PI3K-AKT signaling in many pathological conditions including cancer has attracted much of interest for drug targeting. Various isoforms are known from three classes of PI3K. Targeting selective isoform is advantageous to overcome the global deleterious effects of drug. PI-103 is a specific inhibitor of p110α of class I PI3K. The present study is aimed to analyze anti-carcinogenic activity of PI-103 in Dalton's lymphoma ascite (DLA) cells. Result shows regression in cell proliferation and increased apoptosis in terms of increased Annexin V binding, nuclear fragmentation and active caspase 3 level. It is correlated with attenuation of PI3K-AKT signaling by PI-103 via downregulation of the level of p110α, phospho-p85α, phospho- AKT, and PKCα in DLA cells as well as in H2O2induced DLA cells. Additionally, ROS accumulation is declined in H2O2induced DLA cells. Overall result suggests that PI-103 attenuates PI3K-AKT signaling via induction of apoptosis in murine T-cell lymphoma.
authors.affiliation: a Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science , Banaras Hindu University , Varanasi , India.
authors.forename: Akhilendra Kumar
authors.initials: AK
authors.lastname: Maurya
authors.affiliation: a Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science , Banaras Hindu University , Varanasi , India.
authors.forename: Manjula
authors.initials: M
authors.lastname: Vinayak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005663:Furans; C522973:PI103; D011725:Pyridines; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051571:Protein Kinase C-alpha
keywords: PI-103; PI3K-AKT signaling; apoptosis; lymphoma