TW96, a synthetic 1,4-naphthoquinone, differentially regulates vascular and endothelial cells survival

Yaron Aviv, Sharon Etzion, Thida Win, Shmuel Bittner, Yossi Granot

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Vascular smooth muscle cell (VSMCs) proliferation is an essential factor in cardiovascular diseases, such as primary atherosclerosis and in-stent restenosis. In this study, we examined the effects of the novel synthetic naphthoquinone, 2-pyrrilidino-3-(p-hydroxyphenylamino)-1,4-naphthoquinone (TW-96), on cultured VSMCs and endothelial cells (ECs). Pharmacological concentrations of the derivative TW96 were found to induce VSMCs death, probably by increasing ROS levels while decreasing mitochondrial potential (ΔΨm) without affecting ECs. Treatment of tissue cultures with ROS is known to induce MAPK activity. Our observations showed prolonged phosphorylation and perinuclear accumulation of ERK1/2 and p38 simultaneously with an inhibition of MKP1. Increased expression of Bax found in TW96-stimulated VSMCs was inhibited by the NADPH oxidase inhibitor diphenyliodonium (DPI). An examination of the suppressive effects of TW96 on PDGF-BB-stimulated VSMCs cycle progression showed that TW96 leads to migration arrest at concentrations lower than LC50. We hope that this prototype derivative will establish the basis for creating more specific naphthoquinone derivatives aimed at preventing the VSMCs proliferation associated with stenosis and restenosis.

Original languageEnglish
Pages (from-to)225-235
Number of pages11
JournalVascular Pharmacology
Issue number4
StatePublished - 1 Oct 2009


  • BAX
  • MAPKs
  • Migration arrest
  • Naphthoquinone
  • ROS

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology


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