Abstract
Cortex lycii radicis is the dried root bark of Lycium chinense, a traditional Chinese herb used in multiple ailments. The crude extract of Cortex lycii radicis has growth inhibition effect on GBM cells. Kukoamine A (KuA) is a spermine alkaloid derived from it. KuA possesses antioxidant, anti-inflammatory activities, but its anticancer activity is unknown. In this study, the growth and migration inhibition effect of KuA on human GBM cells and the possible mechanism of its activity were investigated. After KuA treatment, proliferation and colony formation of GBM cells were decreased significantly; apoptotic cells were increased; the cell cycle was arrested G0/G1 phase; the migration and invasion were decreased, the growth of tumors initiated from GBM cells was inhibited significantly; the expressions of 5-Lipoxygenase (5-LOX) were decreased, apoptotic proteins, Bax and caspase-3 were increased, and antiapoptotic protein Bcl-2 was decreased significantly; The expressions of CCAAT/enhancer binding protein β (C/EBPβ), N-cadherin, vimentin, twist and snail+slug were decreased significantly, while the expression of E-cadherin was increased significantly in KuA treated GBM cells and tumor tissues. KuA inhibited human glioblastoma cell growth and migration in vitro and in vivo through apoptosis induction and epithelial-mesenchymal transition attenuation by downregulating expressions of 5-LOX and C/EBPβ.
Highlights
Cortex lycii radicis is the dried root bark of Lycium chinense, a traditional Chinese herb used in multiple ailments
The results demonstrate that Kukoamine A (KuA) inhibited human GBM cell growth selectively in intro
Expressions of 5-LOX and Bcl-2 proteins were decreased significantly; expressions of Bax and active caspase-3 were increased significantly in KuA treated U251cells, WJ1 cells (Fig. 6A–D, p < 0.01) and tumor tissues (Fig. 6I,J, p < 0.01); the expressions of CCAAT/enhancer binding protein β (C/EBPβ), N-cadherin, vimentin, twist and snail+slug were decreased significantly, while the expression of E-cadherin was increased significantly in KuA treated U251cells, WJ1 cells (Fig. 6E–H, p < 0.01) and tumor tissues (Fig. 6K,L, p < 0.01) compared with the controls. These results suggest that KuA inhibited human GBM cell growth through apoptosis induction by decreasing the expressions of 5-Lipoxygenase and Bcl-2, increasing expressions of Bax and active caspaes-3; it suppressed GBM cell migration through epithelial-mesenchymal transition attenuation by downregulating the expressions of C/EBPβ, N-cadherin, vimentin, twist and snail+slug, and upregulating the expression of E-cadherin
Summary
Cortex lycii radicis is the dried root bark of Lycium chinense, a traditional Chinese herb used in multiple ailments. The crude extract of Cortex lycii radicis has growth inhibition effect on GBM cells. The growth and migration inhibition effect of KuA on human GBM cells and the possible mechanism of its activity were investigated. Cortex lycii radicis is the dried root bark of Lycium chinense, a traditional Chinese herb. The crude extract of Cortex lycii radicis has growth inhibition effect on GBM cells (U87MG)[16]. Kukoamine A (KuA), a spermine alkaloid, is a major bioactive component in Cortex lycii radicis. It processes antihypertensive, antioxidant, anti-inflammatory, soybean lipoxygenase inhibition and neuroprotection activities[18,19], and protects neuroblastoma SH-SY5Y cells from H2O2 induced oxidative stress damage[19]
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