Research Papers:

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

Guangwen Shu, Lang Zhang, Shanqing Jiang, Zhuo Cheng, Guan Wang, Xu Huang and Xinzhou Yang _

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Oncotarget. 2016; 7:40285-40296. https://doi.org/10.18632/oncotarget.9603

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Guangwen Shu1, Lang Zhang1, Shanqing Jiang1, Zhuo Cheng1, Guan Wang1, Xu Huang1, Xinzhou Yang1

1School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China

Correspondence to:

Xinzhou Yang, email: [email protected]

Keywords: isoliensinine, hepatocellular carcinoma, PP2A, I2PP2A, NF-κ B

Received: February 15, 2016     Accepted: April 26, 2016     Published: May 26, 2016


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.

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