Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways

Abstract

Thymoquinone, a component derived from the medial plant Nigella sativa, has been used for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on cell proliferation of many cancer cell lines and hormone-refractory prostate cancer by suppressing androgen receptor and E2F-1. Whether thymoquinone inhibits tumor angiogenesis, the critical step of tumor growth and metastasis, is still unknown. In this study, we found that thymoquinone effectively inhibited human umbilical vein endothelial cell migration, invasion, and tube formation. Thymoquinone inhibited cell proliferation and suppressed the activation of AKT and extracellular signal-regulated kinase. Thymoquinone blocked angiogenesis in vitro and in vivo, prevented tumor angiogenesis in a xenograft human prostate cancer (PC3) model in mouse, and inhibited human prostate tumor growth at low dosage with almost no chemotoxic side effects. Furthermore, we observed that endothelial cells were more sensitive to thymoquinone-induced cell apoptosis, cell proliferation, and migration inhibition compared with PC3 cancer cells. Thymoquinone inhibited vascular endothelial growth factor -induced extracellular signal-regulated kinase activation but showed no inhibitory effects on vascular endothelial growth factor receptor 2 activation. Overall, our results indicate that thymoquinone inhibits tumor angiogenesis and tumor growth and could be used as a potential drug candidate for cancer therapy.

Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway

“…It is reported that in prostate cancer PC3 cells, thymoquinone may suppress tumor angiogenesis and growth by downregulating AKT and extracellular signal-regulated kinase (ERK) signaling (17). Additionally, thymoquinone notably suppressed DNA synthesis and proliferation in prostate cancer LNCaP, C4-2B, DU145 and PC3 cell lines via inactivation of the androgen receptor (AR) and E2F1, a regulator of cell viability (18).…”

Cytotoxicity of Nigella Sativa Seed Oil and Extract Against Human Lung Cancer Cell Line

“…cancer diseases, including cervical cancer (Effenberger et al, 2010), blood cancer (El-Mahdy et al, 2005), hepatic cancer (Thabrew et al, 2005), colon cancer (Salim and Fukushima, 2003), pancreatic cancer (Chehl et al, 2009), skin cancer (Salomi et al, 1991), fibrosarcoma (Awad, 2005), renal cancer (Khan and Sultana, 2005), prostate cancer (Yi et al, 2008), and breast cancers (Farah and Begum, 2003;Ahmad et al, 2012). Pharmacologically important components of N sativa extracts have also been studied against lung cancer as an anticancer agent.…”

Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells

“…30 Similarly, Thymoquinone, a phytochemical compound found in the plant Nigella sativa, inhibits tumor angiogenesis and tumor growth by suppressing extracellular signal-regulated kinase signaling pathways. 31 Until now, although antiangiogenic molecules dominantly target endothelial cells and exhibit effective control of tumor angiogenesis, the finding of a natural product-derived single compound to control the tumor mass via the marked delay of tumor angiogenesis, particularly through the modulation of stem/progenitor cells bioactivities, are largely unknown.…”