Targeting Aurora B kinase with Tanshinone IIA Suppresses Tumor Growth and Overcomes Radioresistance

Abstract

Background Aurora B kinase is aberrantly overexpressed in various tumors and shown to be a promising target for anti-cancer therapy. Methods A customized natural product library was used for natural compound screening through Molecular modeling. The expression of Aurora B in oral squamous cell carcinoma (OSCC) and the inhibitory effect of Tanshinone IIA (Tan IIA) on OSCC were examined by MTS and colony formation assays, immunoblot, immunofluorescence, immunohistochemical staining, and in vivo xenograft experiment. Results Aurora B is overexpressed in OSCC tumor tissues and cell lines. Knockdown of Aurora B inhibited the malignant phenotypes of OSCC cells in vitro and in vivo. With a molecular modeling screening of 74 commercially available natural products, we identified that Tan IIA, as a potential Aurora B kinase inhibitor. Tan IIA exhibited a significant anti-tumor effect on OSCC cells both in vitro and in vivo, including reduction of Aurora B and histone H3 phosphorylation, induction of G2/M cell cycle arrest, increase the population of polyploid cells, and promotion of apoptosis. The in vivo mouse model revealed that Tan IIA delayed tumor growth of OSCC cells. Tan IIA alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Conclusion Our data indicates that targeting Aurora B kinase signaling is a promising anti-tumor strategy for OSCC treatment.

Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer

“…Similar to NSCLC, metastatic colorectal cancer patients lived significantly shorter when they had high levels of AURKB expression in their tumor tissues [ 32 ] and the publicly available databases further showed that increased AURKB expression also correlated significantly with reduced survival in breast cancer patients [ 33 ]. AURKB expression has been identified as a prognostic biomarker in glioblastoma [ 34 ], gastric cancer [ 35 ] and oral cancer [ 36 , 37 , 38 ]. AURKB overexpression was found to be increased in prostate cancer tissues compared to healthy controls [ 39 ].…”

Comparative efficacy of five most common traditional Chinese medicine monomers for promoting recovery of motor function in rats with blunt spinal cord injury: a network meta-analysis

“…Almost all GSs have anti-inflammatory and antioxidant properties and thus their medicinal potential is often analyzed together (24). TIIA is a monomer obtained from the liposoluble extract of Salvia miltiorrhiza Bunge (25,26). Animal studies have demonstrated that these five TCM monomers assume a neuroprotective role in blunt SCI through several mechanisms to promote the recovery of motor function.…”