Effects of trimethoxystilbene on proliferation and apoptosis of pulmonary artery smooth muscle cells

Cell Biochem Biophys. 2012 Nov;64(2):101-6. doi: 10.1007/s12013-012-9377-7.

Abstract

Proliferation of pulmonary artery smooth muscle cells (PASMC) is an important contributor to the progress of pulmonary arterial hypertension (PAH). Anti-inflammatory therapies may have therapeutic applicability for PAH. Resveratrol (RES) has prominent anti-inflammatory effects in vitro, but in vivo its beneficial effects are limited by short systemic half life and poor lipotrophy. A derivative of RES, trimethoxystilbene (TMS), has higher lipotropy and extended half life compared with RES, and can potentially overcome the limitations of RES. In the present study, we studied the effects of TMS and RES on proliferation and apoptosis of PASMC stimulated with Tumor Necrosis Factor-α. The effects on PASMC proliferation were quantified by MTT, while apoptosis was assessed by flow cytometry (Annexin V/propidium iodide assay). We observed strong inhibitory effects of TMS on the growth of PASMC, and these effects were 20 times more potent than those of RES. We further documented induction of apoptosis in PASMC treated with TMS, again, to a higher degree than with RES. In conclusion, TMS is more potent than RES in the inhibition of proliferation and induction of apoptosis of PASMC, demonstrating its potentially beneficial role for treating PAH.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation
  • Cell Survival / drug effects
  • Cells, Cultured
  • Flow Cytometry
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypertension / metabolism
  • Hypertension / pathology
  • Inflammation / complications
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Pulmonary Artery / cytology
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism
  • Rats
  • Resveratrol
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • 3,4',5-trimethoxystilbene
  • Anti-Inflammatory Agents
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Resveratrol