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Abstract Title:

Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells.

Abstract Source:

Oncol Lett. 2018 Apr ;15(4):5417-5424. Epub 2018 Feb 15. PMID: 29563994

Abstract Author(s):

Kristina Shilnikova, Mei Jing Piao, Kyoung Ah Kang, Yea Seong Ryu, Jeong Eon Park, Yu Jae Hyun, Ao Xuan Zhen, Yong Joo Jeong, Uhee Jung, In Gyu Kim, Jin Won Hyun

Article Affiliation:

Kristina Shilnikova

Abstract:

Cisplatin-based chemotherapy often results in the development of chemoresistance when used to treat ovarian cancer, which is difficult to overcome. The present study investigated the cytotoxic and anti-migratory effects of shikonin, a naphthoquinone compound, on cisplatin-resistant human ovarian cancer A2780 cells (A2780-CR). Shikonin had a potent dose-dependent cytotoxic effect on A2780-CR cells, with 9µM shikonin treatment reducing A2780-CR cell viability by 50%, validate using an MTT assay. Shikonin induced apoptosis, as evidenced by the increased number of apoptotic bodies, following staining with Hoechst 33342, and terminal deoxynucleotidyl cell transferase dUTP nick end labeling-positive cells following treatment. Flow cytometry and fluorescent microscope imaging, following JC-1 staining, revealed that shikonin increased mitochondrial membrane depolarization. Also it altered the levels of apoptosis-associated proteins, leading to diminished expression of B cell lymphoma-2 (Bcl-2), enhanced expression of Bcl-associated X, and cleavage of caspase-9 and -3, as revealed using western blot analysis. Shikonin activated mitogen-activated protein kinases; while treatment with specific inhibitors of these kinases attenuated the decline in cell viability induced by shikonin treatment. In addition, the cell migration assay and western blot analysis indicated that shikonin decreased the migratory capacity of A2780-CR cells via the upregulation of epithelial-cadherin and downregulation of neural-cadherin. Taken together, the results of the present study indicated that shikonin induces mitochondria-mediated apoptosis and attenuates the epithelial-mesenchymal transition in A2780-CR cells.

Study Type : In Vitro Study

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