Isoliensinine induces dephosphorylation of NF-κB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells: roles of impairing PP2A/I2PP2A interaction

// Guangwen Shu 1 , Lang Zhang 1 , Shanqing Jiang 1 , Zhuo Cheng 1 , Guan Wang 1 , Xu Huang 1 , Xinzhou Yang 1 1 School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China Correspondence to: Xinzhou Yang, email: xinzhou_yang@163.com Keywords: isoliensinine, hepatocellular carcinoma, PP2A, I2PP2A, NF-κ B Received: February 15, 2016      Accepted: April 26, 2016      Published: May 26, 2016 ABSTRACT Our previous study discovered that isoliensinine (isolie) triggers hepatocellular carcinoma (HCC) cell apoptosis via inducing p65 dephosphorylation at Ser536 and inhibition of NF-κB. Here, we showed that isolie promoted p65/PP2A interaction in vitro and in vivo . Repression of PP2A activity or knockdown of the expression of PP2A-C (the catalytic subunit of PP2A) abrogated isolie-provoked p65 dephosphorylation. I2PP2A is an endogenous PP2A inhibitor. Isolie directly impaired PP2A/I2PP2A interaction. Knockdown of I2PP2A boosted p65/PP2A association and p65 dephosphorylation. Overexpression of I2PP2A restrained isolie-induced p65 dephosphorylation. Untransformed hepatocytes were insensitive to isolie-induced NF-κB inhibition and cell apoptosis. In these cells, basal levels of I2PP2A and p65 phosphorylation at Ser536 were lower than in HCC cells. These findings collectively indicated that isolie suppresses NF-κB in HCC cells through impairing PP2A/I2PP2A interaction and stimulating PP2A-dependent p65 dephosphorylation at Ser536.