Date Published: March 18, 2018
Publisher: Tabriz University of Medical Sciences
Author(s): Fatemeh Sheikhbahaei, Mozafar Khazaei, Seyed Noureddin Nematollahi-Mahani.
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.
Angiogenesis targeting has recently been suggested as a promising approach for anticancer therapies.1 Branching of the vascular network and formation of new blood vessels from pre-existing vasculature identified as angiogenesis is considered as a key biological process, which involved physiologic conditions such as embryonic development, endometrial repair, ovulation, and pathologic changes including solid cancers growth, diabetic retinopathy and rheumatoid arthritis.2 It has been suggested that angiogenesis requires the balance between the activation of stimulating and inhibitory molecules that initiate or stop this phenomenon. Owing to this, factors such as hypoxia, decreased pH, increased lactic acid, mutations in oncogene and tumor suppressor genes seem to disturb the balance in an attempt to alter the process of angiogenesis.3 It is evident that in the absence of vascular support, apoptosis and/or necrosis may be activated in tumoral cells. When it is observed that tumor mass is required to achieve more nutrients and oxygen; angiogenesis signaling is stimulated to compensate for deprivation. Hence, inhibition of angiogenesis may be considered as an important way to combat cancer progression.4
Tranilast was purchased from Sigma-Aldrich, (Mo, USA) and dissolved in dimethyl sulfoxide (DMSO) such thatthe final DMSO concentration in experimental wells did not exceed 0.5% (v/v). Dulbecco’s modified Eagle’s medium and Ham’s F12 (DMEM/F12), fetal bovine serum (FBS), trypsin, and acridine orange (AO) were purchased from Sigma-Aldrich Chemical Co (St. Louis, MO, USA). Gene Matrix Universal RNA Purification Kit was purchased from EURx Ltd. Gdansk (Poland ul). PrimeScriptTM 1st strand cDNA Synthesis Kit and SYBR Premix Ex Taq technology were purchased from Takara (Bio Inc. Japan).
In this study, the synergic effect of T. polium, a medicinal plant, and tranilast on HUVECs was studied for the first time. T. polium and tranilast alone, and in combination reduced the viability of HUVECs in a dose-and time-dependent manner. Combined treatment significantly increased cytotoxicity with a combination index value between 0.71 and 0.21, showing synergistic effects of T. polium and tranilast that were in line with LDH assay.
These results showed that T. polium (TP) plus tranilast could be a promising combination therapy for future clinical trials in cancer patients through angiogenesis inhibition. Combination of T.polium and tranilast can induce anti-angiogenic effects on HUVECs, which in turn lead to reduced cell viability, increased apoptosis and decreased migration capacity of these cells. Further in vivo studies and future clinical trials are proposed to evaluate the efficacy of T. polium and tranilast combination therapy for angiogenesis inhibition as a new therapeutic option.
This study was part of Ph.D. thesis. The authors appreciate the financial support of this investigation by Kerman and Kermanshah University of Medical Sciences. The authors would like to thank Radan native english edit for editing the manuscript.
This experimental in vitro study was carried out using HUVECs. This study was approved by ethics committee at Kerman University of Medical Science. Ethical code: IR. KMU.REC.1395.152.
The authors declare that they have no competing interest.