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 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.

Keywords:

• PI-103
• PI3K-AKT signaling
• apoptosis
• lymphoma

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1225207.

Funding

Research was supported by University Grants Commission (UGC), India. M. V. is thankful to UGC-CAS program to Department of Zoology for infrastructural facilities; and Interdisciplinary School of Life Sciences (ISLS), BHU, Varanasi, for providing Flow Cytometry (FACS) facility. A. K. M. thanks CSIR, India, for JRF and SRF (CSIR award no. file no. 09/013(0338)/2010-EMR-I).