Abstract
This study aims to explore the apoptotic function of shikonin on the papillary thyroid cancer cells and the related mechanism. The papillary thyroid cancer cell lines K1 and W3 and thyroid follicular epithelial cells NTHY-ORI 3-1 were treated with different concentrations of shikonin. Cell proliferation was tested. Morphological changes of the apoptotic cells were observed by Hoechst 33342 staining. The apoptosis rate of the papillary thyroid cancer cells was measured with flow cytometry. Changes of the cell cycle were explored. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Bcl-2 family proteins and caspase-3 expression with shikonin treatment was analyzed by real-time fluorescence polymerase chain reaction (PCR). Cell proliferation of K1 and W3 was inhibited by shikonin, and the inhibition was dose–time dependent. Papillary thyroid carcinoma cells treated by shikonin had no obvious cell cycle arrest but were observed with the higher apoptosis rate and the typical apoptotic morphological changes of the cell nucleus. JC-1 staining showed that shikonin reduced the mitochondrial membrane potential of papillary thyroid carcinoma cells. Real-time PCR results showed that shikonin significantly increased Bax and caspase-3 expression and upregulated Bcl-2 expression in a dose-dependent manner in papillary thyroid carcinoma cells. However, the NTHY-ORI 3-1 was almost not affected by shikonin treatment. Shikonin can inhibit K1 and W3 cell proliferation in a dose- and time-dependent manner, enhance Bax levels, reduce anti-apoptotic protein Bcl-2 levels, result in decreasing mitochondrial membrane potential and activating caspase-3 enzyme, and finally lead to apoptosis.
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Acknowledgments
This study was supported by the grants from the Zhejiang Natural Science Foundation (Y2100248), Foundation of Department of Science and Technology of Zhejiang Province (2009C33155), Foundation of Zhejiang Health Department (2009A218), Taizhou Science and Technology Bureau (102KY15), and Zhejiang Province Chinese Medicine Study Foundation (2011ZA113).
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The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.
An erratum to this article can be found online at http://dx.doi.org/10.1007/s13277-017-5487-6.
Chibo Liu and Jiayu Chen contributed equally to this work.
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Liu, C., Yin, L., Chen, J. et al. RETRACTED ARTICLE: The apoptotic effect of shikonin on human papillary thyroid carcinoma cells through mitochondrial pathway. Tumor Biol. 35, 1791–1798 (2014). https://doi.org/10.1007/s13277-013-1238-5
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DOI: https://doi.org/10.1007/s13277-013-1238-5