Cepharanthine inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing expression of vascular endothelial growth factor and interleukin-8

Abstract

Abstract. Cepharanthine is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata, which is widely used for the treatment of many acute and chronic diseases, and can exert antitumor effects on several human cancer cell lines. However, little is known about the detailed mechanisms of the antitumor activity of Cepharanthine. In the present study, we determined whether Cepharanthine could suppress angiogenesis and growth of human oral squamous cell carcinoma (OSCC) cells in vitro and in vivo. Cepharanthine significantly inhibited expression of two major pro-angiogenic molecules, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in cultured cells and in cells implanted into the subcutaneous tissue of nude mice. Also, Cepharanthine inhibited the nuclear factor-κB (NF-κB) activity in human OSCC cells in vitro and in vivo. The decreased expression of VEGF and IL-8 correlated with decreased tumor cell growth and decreased vascularization in vitro and in vivo. These findings suggest that Cepharanthine can suppress angiogenesis and growth of OSCC cells by inhibiting expression of VEGF and IL-8 involved in the blockade of NF-κB activity.

Inhibition of the STAT3 signaling pathway is involved in the antitumor activity of cepharanthine in SaOS2 cells

“…The inflammatory pathways that are important in carcinogenesis include NF-κB, STATs and COX -, and they are promising targets for cancer therapy [31,32] . Previous studies have shown that inactivation of NF-κB is an important mechanism for the antitumor activity of CEP [8,15,16] . SaOS2 is an osteosarcoma cell line in which STAT3 is constitutively activated and plays a crucial role in cell proliferation and survival [10,22,33] .…”

“…Although accumulating evidence has shown that CEP plays a potential role in inhibiting cell growth and inducing apoptosis in many tumors [3] , the underlying mechanism remains elusive. Because CEP is primarily an anti-inflammatory agent, the antitumor activity of CEP is associated with inhibition of inflammation-related signaling pathways, among which NF-κB inactivation is important [8,15,16] . In addition to NF-κB, the signal transducer and activator of transcription protein 3 (STAT3) is another critical inflammatory mediator that links inflammation and cancer [17] .…”

Cysteine-rich intestinal protein 2 ( CRIP2 ) acts as a repressor of NF-κB–mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis

“…It is a prognostic factor and is highly expressed in metastatic cancers, including NPC (22,23). IL-8 is proangiogenic (24) and contributes to a poor prognosis in primary NPC (25). IL-8 has been reported to increase expression of the antiapoptotic protein Bcl-2 in endothelial cells (26) and thus to maintain the angiogenic phenotype of endothelial cells (27).…”

Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice

“…Our finding is supported by the recent report that inactivation of Akt by a dominant negative form of Akt could result in suppression of MMP secretion thus suppression of in vivo pulmonary cancer metastasis. 28 Recently, Harada et al 29 also reported that decreased expression of Akt phosphorylation and FGF-2 was correlated with decreased tumorigenicity and angiogenesis in vivo and such reduced angiogenesis was partly due to the blockade of Akt1 activity. Our results also demonstrated that suppression of Akt1 activity by lentivirus-mediated CTMP overexpression might be responsible for inhibition of tumor progression.…”