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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncol+Lett
2018 ; 15
(4
): 5417-5424
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gab.com Text
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Shikonin induces mitochondria-mediated apoptosis and attenuates
epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer
cells
#MMPMID29563994
Shilnikova K
; Piao MJ
; Kang KA
; Ryu YS
; Park JE
; Hyun YJ
; Zhen AX
; Jeong YJ
; Jung U
; Kim IG
; Hyun JW
Oncol Lett
2018[Apr]; 15
(4
): 5417-5424
PMID29563994
show ga
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.