Browse > Article
http://dx.doi.org/10.14348/molcells.2015.0197

Resveratrol Induces Glioma Cell Apoptosis through Activation of Tristetraprolin  

Ryu, Jinhyun (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Yoon, Nal Ae (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Seong, Hyemin (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Jeong, Joo Yeon (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Kang, Seokmin (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Park, Nammi (Department of Physiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Choi, Jungil (Gyeongnam Department of Environmental Toxicology and Chemistry, Korea Institute of Toxicology (KIT))
Lee, Dong Hoon (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Roh, Gu Seob (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Kim, Hyun Joon (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Cho, Gyeong Jae (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Choi, Wan Sung (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Park, Jae-Yong (School of Biosystem and Biomedical Science, College of Health Science, Korea University)
Park, Jeong Woo (Department of Biological Sciences, University of Ulsan)
Kang, Sang Soo (Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University)
Publication Information
Molecules and Cells / v.38, no.11, 2015 , pp. 991-997 More about this Journal
Abstract
Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of ARE-scontaining mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4'-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetraprolin (TTP). Res increased TTP expression in U87MG human glioma cells. Res-induced TTP destabilized the urokinase plasminogen activator and urokinase plasminogen activator receptor mRNAs by binding to the ARE regions containing the 3' untranslated regions of their mRNAs. Furthermore, TTP induced by Res suppressed cell growth and induced apoptosis in the human glioma cells. Because of its regulation of TTP expression, these findings suggest that the bioactive dietary compound Res can be used as a novel anti-cancer agent for the treatment of human malignant gliomas.
Keywords
apoptosis; glioma; resveratrol; TTP; uPA; uPAR;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Ahmad, N., Adhami, V.M., Afaq, F., Feyes, D.K., and Mukhtar, H. (2001). Resveratrol causes WAF-1/p21-mediated G(1)-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells. Clin. Cancer Res. 7, 1466-1473.
2 Al-Haj, L., Blackshear, P.J., and Khabar, K.S. (2012). Regulation of p21/CIP1/WAF-1 mediated cell-cycle arrest by RNase L and tristetraprolin, and involvement of AU-rich elements. Nucleic Acids Res. 40, 7739-7752.   DOI
3 Al-Souhibani, N., Al-Ahmadi, W., Hesketh, J.E., Blackshear, P.J., and Khabar, K.S. (2010). The RNA-binding zinc-finger protein tristetraprolin regulates AU-rich mRNAs involved in breast cancer-related processes. Oncogene 29, 4205-4215.   DOI
4 Baou, M., Jewell, A., and Murphy, J.J. (2009). TIS11 family proteins and their roles in posttranscriptional gene regulation. J. Biomed. Biotechnol. 2009, 634520.
5 Boocock, D.J., Faust, G.E., Patel, K.R., Schinas, A.M., Brown, V.A., Ducharme, M.P., Booth, T.D., Crowell, J.A., Perloff, M., Gescher, A.J., et al. (2007). Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol. Biomarkers Prev. 16, 1246-1252.   DOI
6 Brennan, S.E., Kuwano, Y., Alkharouf, N., Blackshear, P.J., Gorospe, M., and Wilson, G.M. (2009). The mRNA-destabilizing protein tristetraprolin is suppressed in many cancers, altering tumorigenic phenotypes and patient prognosis. Cancer Res. 69, 5168-5176.   DOI
7 Castino, R., Pucer, A., Veneroni, R., Morani, F., Peracchio, C., Lah, T.T., and Isidoro, C. (2011). Resveratrol reduces the invasive growth and promotes the acquisition of a long-lasting differentiated phenotype in human glioblastoma cells. J. Agric. Food Chem. 59, 4264-4272.   DOI
8 Cottart, C.H., Nivet-Antoine, V., Laguillier-Morizot, C., and Beaudeux, J.L. (2010). Resveratrol bioavailability and toxicity in humans. Mol. Nutr. Food Res. 54, 7-16.   DOI
9 Cucciolla, V., Borriello, A., Oliva, A., Galletti, P., Zappia, V., and Della Ragione, F. (2007). Resveratrol: from basic science to the clinic. Cell Cycle 6, 2495-2510.   DOI
10 Dorai, T., and Aggarwal, B.B. (2004). Role of chemopreventive agents in cancer therapy. Cancer Lett. 215, 129-140.   DOI
11 Fremont, L. (2000). Biological effects of resveratrol. Life Sci. 66, 663-673.   DOI
12 Gondi, C.S., Lakka, S.S., Yanamandra, N., Siddique, K., Dinh, D.H., Olivero, W.C., Gujrati, M., and Rao, J.S. (2003). Expression of antisense uPAR and antisense uPA from a bicistronic adenoviral construct inhibits glioma cell invasion, tumor growth, and angiogenesis. Oncogene 22, 5967-5975.   DOI
13 Gondi, C.S., Kandhukuri, N., Dinh, D.H., Gujrati, M., and Rao, J.S. (2007). Down-regulation of uPAR and uPA activates caspase-mediated apoptosis and inhibits the PI3K/AKT pathway. Int. J. Oncol. 31, 19-27.
14 Jang, M., Cai, L., Udeani, G.O., Slowing, K.V., Thomas, C.F., Beecher, C.W., Fong, H.H., Farnsworth, N.R., Kinghorn, A.D., Mehta, R.G., et al. (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275, 218-220.   DOI
15 Jiang, H., Zhang, L., Kuo, J., Kuo, K., Gautam, S.C., Groc, L., Rodriguez, A.I., Koubi, D., Hunter, T.J., Corcoran, G.B., et al. (2005). Resveratrol-induced apoptotic death in human U251 glioma cells. Mol. Cancer Ther. 4, 554-561.   DOI
16 Li, Y., and Tollefsbol, T.O. (2010). Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components. Curr. Med. Chem. 17, 2141-2151.   DOI
17 Kim, H.K., Kim, C.W., Vo, M.T., Lee, H.H., Lee, J.Y., Yoon, N.A., Lee, C.Y., Moon, C.H., Min, Y.J., Park, J.W., et al. (2012). Expression of proviral integration site for Moloney murine leukemia virus 1 (Pim-1) is post-transcriptionally regulated by tristetraprolin in cancer cells. J. Biol. Chem. 287, 28770-28778.   DOI
18 Lee, H.H., Vo, M.T., Kim, H.J., Lee, U.H., Kim, C.W., Kim, H.K., Ko, M.S., Lee, W.H., Cha, S.J., Min, Y.J., et al. (2010). Stability of the LATS2 tumor suppressor gene is regulated by tristetraprolin. J. Biol. Chem. 285, 17329-17337.   DOI
19 Lee, J.Y., Kim, H.J., Yoon, N.A., Lee, W.H., Min, Y.J., Ko, B.K., Lee, B.J., Lee, A., Cha, H.J., Cho, W.J., et al. (2013). Tumor suppressor p53 plays a key role in induction of both tristetraprolin and let-7 in human cancer cells. Nucleic Acids Res. 41, 5614-5625.   DOI
20 Meeran, S.M., Ahmed, A., and Tollefsbol, T.O. (2010). Epigenetic targets of bioactive dietary components for cancer prevention and therapy. Clin. Epigenetics 1, 101-116.   DOI
21 Nakada, M., Nakada, S., Demuth, T., Tran, N.L., Hoelzinger, D.B., and Berens, M.E. (2007). Molecular targets of glioma invasion. Cell Mol. Life Sci. 64, 458-478.   DOI
22 Nanbu, R., Menoud, P.A., and Nagamine, Y. (1994). Multiple instability-regulating sites in the 3′ untranslated region of the urokinase-type plasminogen activator mRNA. Mol. Cell Biol. 14, 4920-4928.   DOI
23 Papoutsis, A.J., Lamore, S.D., Wondrak, G.T., Selmin, O.I., and Romagnolo, D.F. (2010). Resveratrol prevents epigenetic silencing of BRCA-1 by the aromatic hydrocarbon receptor in human breast cancer cells. J. Nutr. 140, 1607-1614.   DOI
24 Stefanska, B., Rudnicka, K., Bednarek, A., and Fabianowska-Majewska, K. (2010). Hypomethylation and induction of retinoic acid receptor beta 2 by concurrent action of adenosine analogues and natural compounds in breast cancer cells. Eur. J. Pharmacol. 638, 47-53.   DOI
25 Roldan, A.L., Cubellis, M.V., Masucci, M.T., Behrendt, N., Lund, L.R., Dano, K., Appella, E., and Blasi, F. (1990). Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J. 9, 467-474.
26 Ryu, J., Ku, B.M., Lee, Y.K., Jeong, J.Y., Kang, S., Choi, J., Yang, Y., Lee, D.H., Roh, G.S., Kim, H.J., et al. (2011). Resveratrol reduces TNF-alpha-induced U373MG human glioma cell invasion through regulating NF-kappaB activation and uPA/uPAR expression. Anticancer Res. 31, 4223-4230.
27 Ryu, J., Yoon, N.A., Lee, Y.K., Jeong, J.Y., Kang, S., Seong, H., Choi, J., Park, N., Kim, N., Cho, W.J., et al. (2015). Tristetraprolin inhibits the growth of human glioma cells through downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor mRNAs. Mol. Cells 38, 156-162.
28 Stupp, R., Hegi, M.E., Gilbert, M.R., and Chakravarti, A. (2007). Chemoradiotherapy in malignant glioma: standard of care and future directions. J. Clin. Oncol. 25, 4127-4136.   DOI
29 Suswam, E., Li, Y., Zhang, X., Gillespie, G.Y., Li, X., Shacka, J.J., Lu, L., Zheng, L., and King, P.H. (2008). Tristetraprolin down-regulates interleukin-8 and vascular endothelial growth factor in malignant glioma cells. Cancer Res. 68, 674-682.   DOI
30 Tinhofer, I., Bernhard, D., Senfter, M., Anether, G., Loeffler, M., Kroemer, G., Kofler, R., Csordas, A., and Greil, R. (2001). Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2. FASEB J. 15, 1613-1615.   DOI
31 Wang, Q., Xu, J., Rottinghaus, G.E., Simonyi, A., Lubahn, D., Sun, G.Y., and Sun, A.Y. (2002). Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res. 958, 439-447.   DOI
32 Trincheri, N.F., Nicotra, G., Follo, C., Castino, R., and Isidoro, C. (2007). Resveratrol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis 28, 922-931.
33 Tseng, S.H., Lin, S.M., Chen, J.C., Su, Y.H., Huang, H.Y., Chen, C.K., Lin, P.Y., and Chen, Y. (2004). Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats. Clin. Cancer Res. 10, 2190-2202.   DOI
34 Villano, J.L., Seery, T.E., and Bressler, L.R. (2009). Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol. 64, 647-655.   DOI
35 Weng, C.J., Wu, C.F., Huang, H.W., Wu, C.H., Ho, C.T., and Yen, G.C. (2010). Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. J. Agric. Food Chem. 58, 2886-2894.   DOI
36 Young, L.E., Sanduja, S., Bemis-Standoli, K., Pena, E.A., Price, R.L., and Dixon, D.A. (2009). The mRNA binding proteins HuR and tristetraprolin regulate cyclooxygenase 2 expression during colon carcinogenesis. Gastroenterology 136, 1669-1679.   DOI