title: 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.
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.
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Shu
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China.
authors.forename: Lang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China.
authors.forename: Shanqing
authors.initials: S
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, PR China.
authors.forename: Xinzhou
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D020134:Catalytic Domain; D004268:DNA-Binding Proteins; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology; D056488:Histone Chaperones / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D051996:Transcription Factor RelA / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D007546:Isoquinolines; C498143:RELA protein, human; D011994:Recombinant Proteins; C513473:SET protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; C499779:isoliensinine; D012694:Serine; D054648:Protein Phosphatase 2; D053148:Caspase 3
keywords: I2PP2A; NF-κ B; PP2A; hepatocellular carcinoma; isoliensinine