Kushen flavonoids induce apoptosis in tumor cells by inhibition of NF‐κB activation and multiple receptor tyrosine kinase activities

Abstract

In this report, the mechanism of the antitumor activities of Kushen flavonoids (KS-Fs) were explored. KS-Fs and kurarinone (Kur), a single flavonoid compound, were able to induce apoptosis of H460 and Eca-109 cells in vitro and H460 cells in vivo. The apoptosis inducing effect was enhanced in the presence of Taxol. In H460 xenograft mice treated with Kur, down-regulation of Bcl-2 and up-regulation of caspase 8 and caspase 3 in tumors were observed by immunohistochemical staining. In addition, KS-Fs and Kur were able to inhibit TNFalpha-induced NF-kappaB activation in 293 cells mediated by the decreased IkappaBalpha phosphorylation. Further the effects of KS-Fs and Kur on multiple receptor tyrosine kinase activities were explored. In cell-based assays, KS-Fs and Kur inhibited the EGF-induced EGF receptor phosphorylation in A431 cells and a constitutively activated Her-2 in MDA-MB-453s cells. In enzymatic assays, KS-Fs and Kur inhibited KDR, but not PDGF BR activities. In A431 xenograft mice treated with Kur, an inhibition of EGF receptor phosphorylation in tumors was observed. These results reveal a novel mechanism by which KS-Fs induces apoptosis in tumors by acting on multiple cellular targets including the inhibition of NF-kappaB activation and multiple receptor tyrosine kinase activities.

Embelin Sensitizes Acute Myeloid Leukemia Cells to TRAIL through XIAP Inhibition and NF-κB Inactivation

“…On the other hand, TRAIL can activate another signal mediated by the transcription factor NF-jB, leading to transcription of genes known to antagonize the death signaling pathway [15] These two signal pathways function in opposite. Thus, TRAIL-induced apoptosis can be significantly augmented by inhibition of the NF-jB activation pathway [17,18]. Although TRAIL is thought to be a highly promising candidate for cancer treatment, the use of TRAIL has major limits in clinical application for its resistance in a variety of cancer cells [18].…”

Effects of matrine on proliferation and apoptosis of cultured retinoblastoma cells

“…Kushen is an example of one of these unexplored substances. Kushen has been described to have an anti-tumor, anti-inflammatory, anti-viral and anti-arrhythmic effect [1][2][3][4]. Kushen includes matrine, which is an alkaloid with the chemical formula of C 15 H 24 N 20 [5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Effects of Surrounding Temperature on Antimicrobial Air Filters Coated with Sophora flavescens Nanoparticles

“…Previous studies have shown that the major antimicrobial components of S. flavescens are kurarinone, kuraridin, and sophoraflavanone G (De Naeyer et al 2004;Piao et al 2006;Han et al 2007), and antimicrobial activity is related to the quantities of these three major components (Chong et al 2013). However, this chemical composition can be altered by environmental factors, particularly by temperature.…”