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Int. J. Mol. Sci. 2010, 11(6), 2267-2280; doi:10.3390/ijms11062267
Article

Down-Regulation of Telomerase Activity and Activation of Caspase-3 Are Responsible for Tanshinone I-Induced Apoptosis in Monocyte Leukemia Cells in Vitro

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Received: 11 May 2010; Accepted: 21 May 2010 / Published: 26 May 2010
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract: Tanshinone I (Tan-I) is a diterpene quinone extracted from the traditional herbal medicine Salvia miltiorrhiza Bunge . Recently, Tan-I has been reported to have anti-tumor effects. In this study, we investigated the growth inhibition and apoptosis inducing effects of Tan-I on three kinds of monocytic leukemia cells (U937, THP-1 and SHI 1). Cell viability was measured by MTT assay. Cell apoptosis was assessed by flow cytometry (FCM) and AnnexinV/PI staining. Reverse transcriptase polymerase chain reaction (RT-PCR) and PCR–enzyme-linked immunosorbent assay (ELISA) were used to detect human telomerase reverse transcriptase (hTERT) expression and telomerase activity before and after apoptosis.The activity of caspase-3 was determined by Caspase colorimetric assay kit and Western blot analysis. Expression of the anti-apoptotic gene Survivin was assayed by Western blot and Real-time RT-PCR using the ABI PRISM 7500 Sequence Detection System. The resultsrevealed that Tan-I could inhibit the growth of these three kinds of leukemia cells and cause apoptosis in a time- and dose-dependent manner. After treatment by Tan-I for 48 h, Western blotting showed cleavage of the caspase-3 zymogen protein with the appearance of its 17-kD subunit, and a 89-kD cleavage product of poly (ADP-ribose) polymerase (PARP), a known substrate of caspase-3, was also found clearly. The expression of hTERT mRNA as well as activity of telomerase were decreased concurrently in a dose-dependent manner. Moreover, Real-time RT-PCR and Western blot revealed a significant down-regulation of Survivin. We therefore conclude that the induction of apoptosis by Tan-I in monocytic leukemia U937 THP-1 and SHI 1 cells is highly correlated with activation of caspase-3 and decreasing of hTERT mRNA expression and telomerase activity as well as down-regulation of Survivin expression. To our knowledge, this is the first report about the effects of Tan-I on monocytic leukemia cells.
Keywords: Tanshinone I (Tan-I); telomerase; survivin; leukemia Tanshinone I (Tan-I); telomerase; survivin; leukemia
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Liu, X.-D.; Fan, R.-F.; Zhang, Y.; Yang, H.-Z.; Fang, Z.-G.; Guan, W.-B.; Lin, D.-J.; Xiao, R.-Z.; Huang, R.-W.; Huang, H.-Q.; Liu, P.-Q.; Liu, J.-J. Down-Regulation of Telomerase Activity and Activation of Caspase-3 Are Responsible for Tanshinone I-Induced Apoptosis in Monocyte Leukemia Cells in Vitro. Int. J. Mol. Sci. 2010, 11, 2267-2280.

AMA Style

Liu X-D, Fan R-F, Zhang Y, Yang H-Z, Fang Z-G, Guan W-B, Lin D-J, Xiao R-Z, Huang R-W, Huang H-Q, Liu P-Q, Liu J-J. Down-Regulation of Telomerase Activity and Activation of Caspase-3 Are Responsible for Tanshinone I-Induced Apoptosis in Monocyte Leukemia Cells in Vitro. International Journal of Molecular Sciences. 2010; 11(6):2267-2280.

Chicago/Turabian Style

Liu, Xiao-Dan; Fan, Rui-Fang; Zhang, Yong; Yang, Hong-Zhi; Fang, Zhi-Gang; Guan, Wei-Bing; Lin, Dong-Jun; Xiao, Ruo-Zhi; Huang, Ren-Wei; Huang, He-Qing; Liu, Pei-Qing; Liu, Jia-Jun. 2010. "Down-Regulation of Telomerase Activity and Activation of Caspase-3 Are Responsible for Tanshinone I-Induced Apoptosis in Monocyte Leukemia Cells in Vitro." Int. J. Mol. Sci. 11, no. 6: 2267-2280.


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