PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma.

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Maurya AK, Vinayak M

PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma.

Leuk Lymphoma. 2017 May;58(5):1153-1161. doi: 10.1080/10428194.2016.1225207. Epub 2016 Sep 23.

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27658642 [ View in PubMed
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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 p110alpha 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 p110alpha, phospho-p85alpha, phospho- AKT, and PKCalpha in DLA cells as well as in H2O2 induced DLA cells. Additionally, ROS accumulation is declined in H2O2 induced DLA cells. Overall result suggests that PI-103 attenuates PI3K-AKT signaling via induction of apoptosis in murine T-cell lymphoma.

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