TY - JOUR AB - 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 9 µM 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. AD - Department of Biochemistry, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea Department of Bio and Nanochemistry, Kookmin University, Seoul 02707, Republic of Korea Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk 56212, Republic of Korea Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea AU - Shilnikova,Kristina AU - Piao,Mei ,Jing AU - Kang,Kyoung ,Ah AU - Ryu,Yea ,Seong AU - Park,Jeong ,Eon AU - Hyun,Yu ,Jae AU - Zhen,Ao ,Xuan AU - Jeong,Yong ,Joo AU - Jung,Uhee AU - Kim,In ,Gyu AU - Hyun,Jin ,Won DA - 2018/04/01 DO - 10.3892/ol.2018.8065 EP - 5424 IS - 4 JO - Oncol Lett KW - shikonin drug resistance epithelial‑mesenchymal transition human ovarian cancer mitochondria‑mediated apoptosis mitogen‑activated protein kinases PY - 2018 SN - 1792-1074 1792-1082 SP - 5417 ST - Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells T2 - Oncology Letters TI - Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells UR - https://doi.org/10.3892/ol.2018.8065 VL - 15 ER -