2,2'-((1R,3R,4S)-4-methyl-4-vinylcyclohexane-1,3-diyl) bis(prop-2-en-1-amine), a bisamino derivative of ß-Elemene, inhibits glioblastoma growth through downregulation of YAP signaling.

ß-Elemene, a compound extracted from Chinese herb Curcuma wenyujin, has been demonstrated with antitumor effects in various cancers, including glioblastoma (GBM), a primary brain tumor with high morbidity and mortality. In this study, we reported a bisamino derivative of ß-Elemene, 2, 2'-((1R, 3R, 4S)-4-methyl-4-vinylcyclohexane-1, 3-diyl) bis(prop-2-en-1-amine) (compound 1), displayed a better anti-GBM effect than ß-Elemene with lower concentration. GBM cell lines (C6 and U87) were treated with compound 1 and subsequently analyzed by several assays. Compound 1 significantly inhibited the migration of C6 and U87 cells based on wound healing assay, transwell assay and inverted migration assay. Furthermore, colony formation assay, immunostaining and flow cytometry assays revealed that compound 1 significantly inhibited the proliferation of GBM cells. In addition, compound 1 induced the apoptosis of GBM cells. Mechanistically, we found Yes-associated protein (YAP) was down-regulated in compound 1-treated GBM cells, and the overexpression of YAP partially rescued the anti-GBM effects of compound 1. Finally, compound 1 suppresses the GBM growth in xenograft model through inactivation YAP signaling. Taken together, these results reveal that a novel derivative of ß-Elemene, compound 1, exhibits more potent anti-GBM activity than ß-Elemene through inactivating YAP signaling pathway, which will provide novel strategies for the treatment of GBM.

[Effect of autologous bone marrow stem cell transplantation on renal function following renal ischemic-reperfusion in rabbits].

OBJECTIVE: To observe the effect of autologous bone marrow stem cell (BMSC) transplantation via the renal artery on renal function recovery following renal ischemic-reperfusion (I/R) injury in rabbits. METHODS: BMSCs were collected and isolated from rabbits. Twenty-eight rabbits were subjected to renal pedicle clamping for 105 min and randomized subsequently into transplantation group and control group. BMSCs or saline were injected into the kidney via the renal artery, respectively. Before and 1, 3, 5, 7, 14, 21, and 28 days after I/R injury the venous blood was collected to measure the serum levels of SCr and BUN, and the renal tissue was sampled for pathological observation. RESULTS: One and 3 days after I/R injury, serum Cr and BUN levels increased significantly to the highest level in both groups. On the 7th day serum Cr and BUN levels in the transplantation group were lower than those in control group and remained so till the end of the experiment. On the 28th day, the levels of serum Cr (90.1+/-11.1 micromol/L) and BUN (8.0+/-1.5 mmol/L) in the transplantation group were significantly lower than those in the control group (135.6+/-32.5 micromol/L and 10.9+/-2.5 mmol/L, respectively, P<0.05). Pathological observation of the renal tissue revealed renal tubular epithelial cell degeneration, necrosis and abscission. CONCLUSION: BMSC transplantation can accelerate renal function repair after acute tubular necrosis resulting from I/R injury, and decrease serum Cr and BUN levels in early stage following the injury.