Fatemeh Sheikhbahaei
1, Mozafar Khazaei
2, Seyed Noureddin Nematollahi-Mahani
3*1 Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
2 Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
3 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Abstract
Purpose: Angiogenesis plays
an important role in numerous pathophysiological events like cancer. As a
result of this, tranilast as an anti-fibrotic drug induces the promising
antitumor activities through the inhibition of angiogenesis. Further, Teucrium polium (TP) is a herbal
medicine (family Lamaceae) with
antitumor properties. This study was
conducted to investigate the combination effects of tranilast and T. polium on
human umbilical vein endothelial cells (HUVECs) viability and apoptotic genes
expression.
Methods: The HUVECs line
was treated using different doses of tranilast and T. polium alone or
their combination. The cell cytotoxicity was evaluated using MTT and LDH
assays; apoptosis was examined using acridine orange/ethidium bromide staining,
nitric oxide (NO) production was evaluated using Griess reaction and the
expression of BAX and BCL-2 genes were detected using
real-time RT-PCR. One-way analysis of variance (ANOVA) test was used to compare
the data in different groups.
Results: The survival rate
of HUVECs was significantly reduced (p<0.05) in a dose dependent manner by
tranilast and T. polium. However, T.
polium and tranilast combination significantly (p<0.001) reduced cell
viability and increased apoptotic cells as compared to each drug alone. Also,
HUVECs treated with Tranilast / T. polium combination showed a reduced
level of NO as regards to cells exposed only to Tranilast or T. polium (p<0.05).
Furthermore, a significant increase in BAX
and a decrease in BCL-2 mRNA
expression were observed in combination group (p<0.001).
Conclusion: T. polium synergistically
increased the antiangiogenic effect of tranilast on in vitro angiogenic
model of HUVECs.