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

Xiao-Dan Liu 1,† email, Rui-Fang Fan 1,† email, Yong Zhang 2,† email, Hong-Zhi Yang 3 email, Zhi-Gang Fang 1 email, Wei-Bing Guan 3 email, Dong-Jun Lin 1 email, Ruo-Zhi Xiao 1 email, Ren-Wei Huang 1 email, He-Qing Huang 4 email, Pei-Qing Liu 4 email and Jia-Jun Liu 1,* email
1 Hematological Department & Institute, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China 2 Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China 3 Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China 4 Lab of Pharmacology and Toxicology, School of Pharmaceutical Science of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China † These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
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

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Cite This Article

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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