Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway

Abstract

Thymoquinone (TQ), the predominant bioactive constituent derived from the medicinal spice Nigella sativa (also known as black cumin), has been applied for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on the cell proliferation of several cancer cell lines. This study was performed to investigate the antitumor and anti-angiogenic effects of thymoquinone on osteosarcoma in vitro and in vivo. Our results showed that thymoquinone induced a higher percentage of growth inhibition and apoptosis in the human osteosarcoma cell line SaOS-2 compared to that of control, and thymoquinone significantly blocked human umbilical vein endothelial cell (HUVEC) tube formation in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and western blot analysis, and found that thymoquinone significantly downregulated NF-κB DNA-binding activity, XIAP, survivin and VEGF in SaOS-2 cells. Moreover, the expression of cleaved caspase-3 and Smac were upregulated in SaOS-2 cells after treatment with thymoquinone. In addition to these in vitro results, we also found that thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing NF-κB and its regulated molecules. Collectively, our results demonstrate that thymoquinone effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Moreover, inhibition of NF-κB and downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of thymoquinone in osteosarcoma.

A review on therapeutic potential of Nigella sativa: A miracle herb

“…It was concluded that TQ effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Therefore, inhibition of NF-κB and downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of TQ in osteosarcoma [57] .…”

Anticancer and anti-angiogenesis effect of the leaf extract of <i>Sargassum wightii</i> against osteosarcoma cancer cells

“…In this study, it was observed that ethanolic leaf extract of marine alga S. wightii effectively inhibited HUVEC cell tube formation. Recent study reported by Peng et al, 2013 confirmed that a phytochemical, thymoquinone from Nigella sativa can inhibit tumor angiogenesis and was able to prevent osteosarcoma cell growth in a mouse osteosarcoma model.…”

“…The inhibitory effect of the ethanolic leaf extract of S. wightii on the viability of osteosarcoma cells was performed as reported previously (Peng et al, 2013). In brief, SaOS-2 cells were seed cultured at the density of 3 × 10 3 cells per well in a 96-well culture plate for overnight.…”

Antitumor and Antiangiogenic Effects of the Crude Oil of Nigella sativa L. in Tumor Tissues in BALB/c Mice

“…Moreover, ROS seem to trigger VEGF expression and the activation of VEGF receptor 2 as well as HIF-1 (hypoxia induced factor-1) induction which consequently stimulates angiogenesis. Hence, by improving antioxidant activity, N. sativa indirectly exerts antiangiogenic effects as well [34]. Endostatin is reportedly responsible, as the major factor, for inhibition of angiogenesis and seems to suppress endothelial cells' proliferation and migration by affecting a variety of genes involved in cell cycle, anti-apoptosis and mitosis.…”