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Published in: Tumor Biology 3/2014

01-03-2014 | Research Article

RETRACTED ARTICLE: The apoptotic effect of shikonin on human papillary thyroid carcinoma cells through mitochondrial pathway

Authors: Chibo Liu, Lihui Yin, Jiaqi Chen, Jiayu Chen

Published in: Tumor Biology | Issue 3/2014

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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.
Literature
1.
go back to reference Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006. Thyroid. 2011;21(2):125–34.CrossRefPubMedPubMedCentral Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006. Thyroid. 2011;21(2):125–34.CrossRefPubMedPubMedCentral
2.
go back to reference Han W, Xie J, Fang Y, Wang Z, Pan H. Nec-1 enhances shikonin-induced apoptosis in leukemia cells by inhibition of RIP-1 and ERK1/2. Int J Mol Sci. 2012;13(6):7212–25.CrossRefPubMedPubMedCentral Han W, Xie J, Fang Y, Wang Z, Pan H. Nec-1 enhances shikonin-induced apoptosis in leukemia cells by inhibition of RIP-1 and ERK1/2. Int J Mol Sci. 2012;13(6):7212–25.CrossRefPubMedPubMedCentral
3.
go back to reference Gong K, Li W. Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: a potential new treatment for hepatocellular carcinoma. Free Radic Biol Med. 2011;51(12):2259–71.CrossRefPubMed Gong K, Li W. Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: a potential new treatment for hepatocellular carcinoma. Free Radic Biol Med. 2011;51(12):2259–71.CrossRefPubMed
4.
go back to reference Sasi N, Hwang M, Jaboin J, Csiki I, Lu B. Regulated cell death pathways: new twists in modulation of Bcl-2 family function [J]. Mol Cancer Ther. 2009;8(6):1421–9.CrossRefPubMedPubMedCentral Sasi N, Hwang M, Jaboin J, Csiki I, Lu B. Regulated cell death pathways: new twists in modulation of Bcl-2 family function [J]. Mol Cancer Ther. 2009;8(6):1421–9.CrossRefPubMedPubMedCentral
5.
go back to reference Hsu P, Huang Y, Tsai M, Wang YJ, Lin JK, Pan MH. Induction of apoptosis by shikonin through coordinative modulation of the Bcl-2 family, p27, and p53, release of cytochrome c and sequential activation of caspases in human colorectal carcinoma cells. J Agric Food Chem. 2004;52(20):6330–7.CrossRefPubMed Hsu P, Huang Y, Tsai M, Wang YJ, Lin JK, Pan MH. Induction of apoptosis by shikonin through coordinative modulation of the Bcl-2 family, p27, and p53, release of cytochrome c and sequential activation of caspases in human colorectal carcinoma cells. J Agric Food Chem. 2004;52(20):6330–7.CrossRefPubMed
6.
go back to reference Salvioli S, Ardizzoni A, Franceschi C, Cossarizza A. JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett. 1997;411(1):77–82.CrossRefPubMed Salvioli S, Ardizzoni A, Franceschi C, Cossarizza A. JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett. 1997;411(1):77–82.CrossRefPubMed
7.
go back to reference Kretschmer N, Rinner B, Deutsch AJ, Lohberger B, Knausz H, Kunert O, et al. Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma cells. J Nat Prod. 2012;75(5):865–9.CrossRefPubMedPubMedCentral Kretschmer N, Rinner B, Deutsch AJ, Lohberger B, Knausz H, Kunert O, et al. Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma cells. J Nat Prod. 2012;75(5):865–9.CrossRefPubMedPubMedCentral
8.
go back to reference Chang IC, Huang YJ, Chiang TI, Yeh CW, Hsu LS. Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells. Biol Pharm Bull. 2010;33(5):816–24.CrossRefPubMed Chang IC, Huang YJ, Chiang TI, Yeh CW, Hsu LS. Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells. Biol Pharm Bull. 2010;33(5):816–24.CrossRefPubMed
9.
go back to reference Fan Y, Jin S, He J, Shao Z, Yan J, Feng T, et al. Effect of β,β-dimethylacrylshikonin on inhibition of human colorectal cancer cell growth in vitro and in vivo. Int J Mol Sci. 2012;13(7):9184–93.CrossRefPubMedPubMedCentral Fan Y, Jin S, He J, Shao Z, Yan J, Feng T, et al. Effect of β,β-dimethylacrylshikonin on inhibition of human colorectal cancer cell growth in vitro and in vivo. Int J Mol Sci. 2012;13(7):9184–93.CrossRefPubMedPubMedCentral
10.
go back to reference Elumalai P, Gunadharini DN, Senthilkumar K, Banudevi S, Arunkumar R, Benson CS, et al. Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway. Toxicol Lett. 2012;215(2):131–42.CrossRefPubMed Elumalai P, Gunadharini DN, Senthilkumar K, Banudevi S, Arunkumar R, Benson CS, et al. Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway. Toxicol Lett. 2012;215(2):131–42.CrossRefPubMed
11.
go back to reference Lu L, Qin A, Huang H, Zhou P, Zhang C, Liu N, et al. Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition. Eur J Pharmacol. 2011;658(2–3):242–7.CrossRefPubMedPubMedCentral Lu L, Qin A, Huang H, Zhou P, Zhang C, Liu N, et al. Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition. Eur J Pharmacol. 2011;658(2–3):242–7.CrossRefPubMedPubMedCentral
13.
go back to reference Abe H, Yoshizaki F. In vitro antifungal activity of naphthoquinone derivatives. Biol Pharm Bull. 2002;25(5):669–70.CrossRefPubMed Abe H, Yoshizaki F. In vitro antifungal activity of naphthoquinone derivatives. Biol Pharm Bull. 2002;25(5):669–70.CrossRefPubMed
14.
go back to reference Gao H, Liu L, Qu ZY, Wei FX, Wang SQ, Chen G, et al. Anti-adenovirus activities of shikonin, a component of Chinese herbal medicine in vitro. Biol Pharm Bull. 2011;34(2):197–202.CrossRefPubMed Gao H, Liu L, Qu ZY, Wei FX, Wang SQ, Chen G, et al. Anti-adenovirus activities of shikonin, a component of Chinese herbal medicine in vitro. Biol Pharm Bull. 2011;34(2):197–202.CrossRefPubMed
15.
go back to reference Andújar I, Ríos JL, Giner RM, Recio MC. Shikonin promotes intestinal wound healing in vitro via induction of TGF-β release in IEC-18 cells. Eur J Pharm Sci. 2013;49(4):637–41.CrossRefPubMed Andújar I, Ríos JL, Giner RM, Recio MC. Shikonin promotes intestinal wound healing in vitro via induction of TGF-β release in IEC-18 cells. Eur J Pharm Sci. 2013;49(4):637–41.CrossRefPubMed
16.
go back to reference Kontogiannopoulos KN, Assimopoulou AN, Hatziantoniou S, Karatasos K, Demetzos C, Papageorgiou VP. Chimeric advanced drug delivery nano systems (chi-aDDnSs) for shikonin combining dendritic and liposomal technology. Int J Phann. 2012;422(1–2):381–9.CrossRef Kontogiannopoulos KN, Assimopoulou AN, Hatziantoniou S, Karatasos K, Demetzos C, Papageorgiou VP. Chimeric advanced drug delivery nano systems (chi-aDDnSs) for shikonin combining dendritic and liposomal technology. Int J Phann. 2012;422(1–2):381–9.CrossRef
17.
go back to reference Yin SY, Peng AP, Huang LT, Wang YT, Lan CW, Yang NS. The phytochemical shikonin stimulates epithelial-mesenchymal transition (EMT) in skin wound healing. Evid Based Complement Alternat Med. 2013;2013:262796.PubMedPubMedCentral Yin SY, Peng AP, Huang LT, Wang YT, Lan CW, Yang NS. The phytochemical shikonin stimulates epithelial-mesenchymal transition (EMT) in skin wound healing. Evid Based Complement Alternat Med. 2013;2013:262796.PubMedPubMedCentral
18.
go back to reference Sankawa U, Ebizuka Y, Miyazaki T, Isomura Y, Otsuka H. Antitumor activity of shikonin and its derivatives. Chem Pharm Bull (Tokyo). 1977;25(9):2392–5.CrossRefPubMed Sankawa U, Ebizuka Y, Miyazaki T, Isomura Y, Otsuka H. Antitumor activity of shikonin and its derivatives. Chem Pharm Bull (Tokyo). 1977;25(9):2392–5.CrossRefPubMed
19.
go back to reference Sankawa U, Otsuka H, Kataoka Y, Iitaka Y, Hoshi A, Kuretani K. Antitumor activity of shikonin, alkannin and their derivatives. II. X-ray analysis of cyclo-alkannin leucoacetate, tautomerism of alkannin and cyclo-alkannin and antitumor activity of alkannin derivatives. Chem Pharm Bull (Tokyo). 1981;29(1):116–2.CrossRef Sankawa U, Otsuka H, Kataoka Y, Iitaka Y, Hoshi A, Kuretani K. Antitumor activity of shikonin, alkannin and their derivatives. II. X-ray analysis of cyclo-alkannin leucoacetate, tautomerism of alkannin and cyclo-alkannin and antitumor activity of alkannin derivatives. Chem Pharm Bull (Tokyo). 1981;29(1):116–2.CrossRef
Metadata
Title
RETRACTED ARTICLE: The apoptotic effect of shikonin on human papillary thyroid carcinoma cells through mitochondrial pathway
Authors
Chibo Liu
Lihui Yin
Jiaqi Chen
Jiayu Chen
Publication date
01-03-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1238-5

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