Dual roles of oxostephanine as an Aurora kinase inhibitor and angiogenesis suppressor

Tran,Thu-Hien Thi; Vu,Le-Duy Ba; Nguyen,Huy Quoc; Pham,Hanh Bich; Do,Xuan-Phuong Thi; Than,Uyen Thi Trang; Pham,Thu-Huong Thi; Do,Linh Dieu; Le,Kim-Van Thi; Nguyen,Thao Phuong; Hoang,My-Nhung Thi

doi:10.3892/ijmm.2022.5189

Dual roles of oxostephanine as an Aurora kinase inhibitor and angiogenesis suppressor

Authors:
- Thu-Hien Thi Tran
- Le-Duy Ba Vu
- Huy Quoc Nguyen
- Hanh Bich Pham
- Xuan-Phuong Thi Do
- Uyen Thi Trang Than
- Thu-Huong Thi Pham
- Linh Dieu Do
- Kim-Van Thi Le
- Thao Phuong Nguyen
- My-Nhung Thi Hoang
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Affiliations: Department of Pharmacognosy, Vietnam University of Traditional Medicine, Hanoi 10000, Vietnam, Department of Cell Biology, Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi 10000, Vietnam, Center of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi 10000, Vietnam, The Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University, Hanoi 10000, Vietnam, Faculty of Apothecary, National Institute of Medicinal Materials, Hanoi 10000, Vietnam, Institute of Marine Biochemistry, Vietnam Academy of Science and Technology, Hanoi 10000, Vietnam
Published online on: September 13, 2022 https://doi.org/10.3892/ijmm.2022.5189
Article Number: 133
Copyright: © Tran et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Aurora kinases, including Aurora A, B and C, play critical roles in cell division. They have been found overexpressed in a number of types of cancer and may thus be potential targets in cancer therapy. Several Aurora kinase inhibitors have been identified and developed. Some of these have been used in clinical trials and have exhibited certain efficacy in cancer treatment. However, none of these has yet been applied clinically due to the poor outcomes. Oxostephanine is an aporphine alkaloid isolated from several plants of the genus Stephania. This compound has been reported to inhibit Aurora kinase activity in kinase assays and in cancer cells. The present study aimed to investigate the real‑time effects of oxostephanine extracted from Stephania dielsiana Y.C. Wu leaves on the growth of an ovarian cancer cell line (OVCAR‑8, human ovarian carcinoma); these effects were compared to those of the well‑known Aurora kinase inhibitor, VX‑680. The effects of oxostephanine on stromal cells, as well as endothelial cells were also examined. The results demonstrated that oxostephanine was an Aurora kinase inhibitor through the prevention of histone H3 phosphorylation at serine 10, the mislocalization of Aurora B and the induction of aneuploidy. Moreover, this substance was selectively cytotoxic to human umbilical vein endothelial cells (hUVECs), whereas it was less cytotoxic to human fibroblasts and umbilical cord‑derived mesenchymal stem cells. In addition, this compound significantly attenuated the migration and tube formation ability of hUVECs. Taken together, the present study demonstrates that oxostephanine plays dual roles in inhibiting Aurora kinase activity and angiogenesis. Thus, it may have potential for use as a drug in cancer treatment.

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