Deguelin, an Aurora B Kinase Inhibitor, Exhibits Potent Anti-Tumor Effect in Human Esophageal Squamous Cell Carcinoma

Abstract

Aurora B kinase has emerged as a key regulator of mitosis and deregulation of Aurora B activity is closely related to the development and progression of human cancers. In the present study, we found that Aurora B is overexpressed in human esophageal squamous cell carcinoma (ESCC), high levels of Aurora B protein were associated with a worse overall survival rate in ESCC patients. Depleting of Aurora B blunted the malignant phenotypes in ESCC cells. Importantly, we demonstrated that a natural compound, deguelin, has a profound anti-tumor effect on ESCC via inhibiting Aurora B activity. Deguelin potently inhibited in vitro Aurora B kinase activity. The in silico docking study further indicated that deguelin was docked into the ATP-binding pocket of Aurora B. Inhibition of Aurora B activity attenuated growth of ESCC cells, resulted in G2/M cell cycle arrest, polyploidy cells formation, and apoptosis induction. Knocking down of Aurora B decreased the sensitivity of ESCC cells to deguelin. The in vivo results showed that deguelin blocked the phosphorylation of histone H3 and inhibited the growth of ESCC tumor xenografts. Overall, we identified deguelin as an effective Aurora B inhibitor, which deserves further studies in other animal models and ESCC treatment.

Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

“…Western blotting was performed as previously described (19). Briefly, A total of 30 μg WCE was mixed with loading buffer and boiled at 95°C for 5 min, followed by SDS-PAGE electrophoresis and electrotransfer.…”

Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3β/FBW7-mediated Mcl-1 destabilization

“…Accumulating evidence reveals that the natural product deguelin exhibits profound anti-cancer potentials in multiple human cancer models, including lung cancer 14 , hepatocellular carcinoma 15 , colorectal cancer 16 , esophageal carcinoma 17 , metastatic melanoma 18 , and breast cancer 19 . The molecular mechanism studies showed that delay of cell cycle progression by inhibition of Aurora B kinase, regulation of metabolisms, such as suppression of glycolysis, down-regulation of angiogenesis and metastasis, and activation of intrinsic apoptosis were related to deguelin-mediated anti-tumor effect [20][21][22] .…”

Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells

“…In contrast to the small molecule through rational chemical design, natural products have more potential to be applied to tumor chemotherapy owing to their structural diversity. Recently, numerous natural compounds have been demonstrated exerting anti-tumor activity through the suppression of cell cycle progression, impairment of angiogenesis, induction of apoptosis, and inhibition of glycolysis [20,[29][30][31][32][33][34]. Piperlongumine is an amide alkaloid constituent of the Piper longum L. (long piper), which is also named as piplartine and used as an Ayurvedic medicine for a long time.…”