Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade

Yu Ying Chen, Cheng Ying Hsieh, Thanasekaran Jayakumar, Kuan Hung Lin, Duen Suey Chou, Wan-Jung Lu, Ming Jen Hsu, Joen Rong Sheu

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The abnormal growth of vascular smooth muscle cells (VSMCs) is considered a critical pathogenic process in inflammatory vascular diseases. We have previously demonstrated that protein phosphatase 2 A (PP2A)-mediated NF-κB dephosphorylation contributes to the anti-inflammatory properties of andrographolide, a novel NF-κB inhibitor. In this study, we investigated whether andrographolide causes apoptosis, and characterized its apoptotic mechanisms in rat VSMCs. Andrographolide activated the p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. Phosphorylated p53 subsequently transactivated the expression of Bax, a pro-apoptotic protein. Transfection with pp2a small interfering RNA (siRNA) suppressed andrographolide-induced p38MAPK activation, p53 phosphorylation, and caspase 3 activation. Andrographolide also activated the Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1), and induced PP2A dephosphorylation, both of which were inhibited by the SHP-1 inhibitor sodium stibogluconate (SSG) or shp-1 siRNA. SSG or shp-1 siRNA prevented andrographolide-induced apoptosis. These results suggest that andrographolide activates the PP2A-p38MAPK-p53-Bax cascade, causing mitochondrial dysfunction and VSMC death through an SHP-1-dependent mechanism.

Original languageEnglish
Article number5651
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - Jul 10 2014

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Non-Receptor Type 6 Protein Tyrosine Phosphatase
Protein Phosphatase 2
p38 Mitogen-Activated Protein Kinases
Vascular Smooth Muscle
Smooth Muscle Myocytes
Apoptosis
Antimony Sodium Gluconate
Small Interfering RNA
Phosphorylation
Apoptosis Regulatory Proteins
src Homology Domains
andrographolide
Vascular Diseases
Caspase 3
Transfection
Cell Death
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade. / Chen, Yu Ying; Hsieh, Cheng Ying; Jayakumar, Thanasekaran; Lin, Kuan Hung; Chou, Duen Suey; Lu, Wan-Jung; Hsu, Ming Jen; Sheu, Joen Rong.

In: Scientific Reports, Vol. 4, 5651, 10.07.2014.

Research output: Contribution to journalArticle

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