Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells

Hong, Young-Bin;Kang, Hyo-Jin;Kim, Hee-Jeong;Rosen, Eliot M.;Dakshanamurthy, Sivanesan;Rondanin, Riccardo;Baruchello, Riccardo;Grisolia, Giuseppina;Daniele, Simoni;Bae, In-Soo

  • Published : 20090300
⟨ Previous Next ⟩

Abstract

Resveratrol has been reported to possess cancer preventive properties. In this study, we analyzed anti-tumor activity of a newly synthesized resveratrol analog, cis-3,4',5-trimethoxy-3'-hydroxystilbene (hereafter called 11b) towards breast and pancreatic cancer cell lines. 11b treatments reduced the proliferation of human pancreatic and breast cancer cells, arrested cells in the G2/M phase, and increased the percentage of cells in the subG1/G0 fraction. The 11b treatments also increased the total levels of mitotic checkpoint proteins such as BubR1, Aurora B, Cyclin B, and phosphorylated histone H3. Mechanistically, 11b blocks microtubule polymerization in vitro and it disturbed microtubule networks in both pancreatic and breast cancer cell lines. Computational modeling of the 11b-tubulin interaction indicates that the dimethoxyphenyl group of 11b can bind to the colchicine binding site of tubulin. Our studies show that the 11b treatment effects occur at lower concentrations than similar effects associated with resveratrol treatments and that microtubules may be the primary target for the observed effects of 11b. These studies suggest that 11b should be further examined as a potentially potent clinical chemotherapeutic agent for treating pancreatic and breast cancer patients.

Keywords

References

  1. Adams RR, Carmena M, Earnshaw WC. Chromosomal passengers and the aurora ABCs of mitosis. Trends Cell Biol 2001;11:49-54 https://doi.org/10.1016/S0962-8924(00)01880-8
  2. Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol 2007; 224:274-83 https://doi.org/10.1016/j.taap.2006.12.025
  3. Azios NG, Krishnamoorthy L, Harris M, Cubano LA, Cammer M, Dharmawardhane SF. Estrogen and resveratrol regulate Rac and Cdc42 signaling to the actin cytoskeleton of metastatic breast cancer cells. Neoplasia 2007;9:147-58 https://doi.org/10.1593/neo.06778
  4. Bae I, Fan S, Meng Q, Rih JK, Kim HJ, Kang HJ, Xu J, Goldberg ID, Jaiswal AK, Rosen EM. BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res 2004;64:7893-909 https://doi.org/10.1158/0008-5472.CAN-04-1119
  5. Bae I, Rih JK, Kim HJ, Kang HJ, Haddad B, Kirilyuk A, Fan S, Avantaggiati ML, Rosen EM. BRCA1 regulates gene expression for orderly mitotic progression. Cell Cycle 2005; 11:1641-66 https://doi.org/10.4161/cc.4.11.2152
  6. Bai R, Pei XF, Boye O, Getahun Z, Grover S, Bekisz J, Nguyen NY, Brossi A, Hamel E. Identification of cysteine 354 of $\beta$-tubulin as part of the binding site for the A ring of colchicine. J Biol Chem 1996;271:12639-45 https://doi.org/10.1074/jbc.271.21.12639
  7. Berendsen HJC, Postma JPM, Vangunsteren WF, Dinola A, Haak AR. Molecular-dynamics with coupling to an external bath. J Chem Phys 1984;81:3684-90 https://doi.org/10.1063/1.448118
  8. Buzdar AU. Preoperative Chemotherapy Treatment of Breast Cancer-A Review. Cancer 2007;110:2394-407 https://doi.org/10.1002/cncr.23083
  9. Case DA, Darden TA, Cheatham TE, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Pearlman DA, Crowley M, Walker RC, Zhang W, Wang B, Hayik S, Roitberg A, Seabra G, Wong KF, Paesani F, Wu X, Brozell S, Tsui V, Gohlke H, Yang L, Tan C, Mongan J, Hornak V, Cui G, Beroza P, Mathews DH, Schafmeister C, Ross WS, Kollman PA, AMBER 9, 2006, University of California, San Francisco
  10. Chen RH. BubR1 is essential for kinetochore localization of other spindle checkpoint proteins and its phosphorylation requires Mad1. J Cell Biol 2002;158:487-96 https://doi.org/10.1083/jcb.200204048
  11. Cuschieri L, Nguyen T, Vogel J. Control at the cell center: the role of spindle poles in cytoskeletal organization and cell cycle regulation. Cell Cycle 2007;6:2788-94 https://doi.org/10.4161/cc.6.22.4941
  12. Darden T, York D, Pedersen L. Particle mesh Ewald: an N.Log(N) method for Ewald sums in large systems. J Chem Phys 1993;98:10089-92 https://doi.org/10.1063/1.464397
  13. Ding XZ, Adrian TE. Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Pancreas 2002;25:71-6 https://doi.org/10.1097/00006676-200211000-00024
  14. Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, Kuten A. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol 2002;81:138-43 https://doi.org/10.1002/jso.10159
  15. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr, Vreven T, Kudin KN, Burant JC. Gaussian 03, 2003, Gaussian, Inc., Pittsburgh, PA
  16. Gorman AM, Bonfoco E, Zhivotovsky B, Orrenius S, Ceccatelli S. Cytochrome c release and caspase-3 activation during colchicine-induced apoptosis of cerebellar granule cells. Eur J Neurosci 1999;11:1067-72 https://doi.org/10.1046/j.1460-9568.1999.00512.x
  17. Hanson RN, Lee CY, Friel CJ, Dilis R, Hughes A, DeSombre ER. Synthesis and evaluation of 17$\alpha$-20E-21-(4-substituted phenyl)-19-norpregna-1,3,5(10),20-tetraene-3,17$\beta$-diols as probes for the estrogen receptor hormone binding domain. J Med Chem 2003;46:2865-76 https://doi.org/10.1021/jm0205806
  18. Ikegami R, Zhang J, Rivera-Bennetts AK, Yager TD. Activation of the metaphase checkpoint and an apoptosis programme in the early zebrafish embryo, by treatment with the spindle-destabilising agent nocodazole. Zygote 1997;5:329-50 https://doi.org/10.1017/S0967199400003919
  19. Ishii H, Okada S, Tokuuye K, Nose H, Okusaka T, Yoshimori M, Nagahama H, Sumi M, Kagami Y, Ikeda H. Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. Cancer 1997;79:1516-20 https://doi.org/10.1002/(SICI)1097-0142(19970415)79:8<1516::AID-CNCR11>3.0.CO;2-0
  20. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CWW, Fong HHS, Farnsworth NR, Kinghorn AD, Menta RG, Moon RC, Pezzuto JM. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275:218-20 https://doi.org/10.1126/science.275.5297.218
  21. Jimeno A, Hidalgo M. Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer. Mol Cancer Ther 2006;5:787-96 https://doi.org/10.1158/1535-7163.MCT-06-0005
  22. Kim EY, Hong YB, Go SH, Lee B, Jung SC. Downregulation of neurotrophic factors in the brain of a mouse model of Gaucher disease; implications for neuronal loss in Gaucher disease. Exp Mol Med 2006;38:348-56 https://doi.org/10.1038/emm.2006.41
  23. Kim R, Saif MW. Is there an Optimal Neoadjuvant Therapy for Locally Advanced Pancreatic Cancer? J Pancreas 2007; 8:279-88
  24. Kong Y, Grembecka J, Edler MC, Hamel E, Mooberry SL, Sabat M, Rieger J, Brown ML. Structure-based discovery of a boronic acid bioisostere of combretastatin A-4. Chem Biol 2005;12:1007-14 https://doi.org/10.1016/j.chembiol.2005.06.016
  25. Kuroiwa Y, Nishikawa A, Kitamura Y, Kanki K, Ishii Y, Umemura T, Hirose M. Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters. Cancer Lett 2006;241:275-80 https://doi.org/10.1016/j.canlet.2005.10.028
  26. Lawrence NJ, McGown AT. The chemistry and biology of antimitotic chalcones and related enone systems. Curr Pharm Des 2005;11:1679-93 https://doi.org/10.2174/1381612053764733
  27. Le Corre L, Chalabi N, Delort L, Bignon YJ, Bernard-Gallon DJ. Resveratrol and breast cancer chemoprevention: molecular mechanism. Mol Nutr Food Res 2005;49:462-71 https://doi.org/10.1002/mnfr.200400094
  28. Lockhart AC, Rothenberg ML, Berlin JD. Treatment for pancreatic cancer: current therapy and continued progress. Gastroenterology 2005;128:1642-54 https://doi.org/10.1053/j.gastro.2005.03.039
  29. Nogales E, Wolf SG, Downing KH. Structure of the alpha beta tubulin dimer by electron crystallography. Nature 1998;391:199-203 https://doi.org/10.1038/34465
  30. Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M. Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res 2002;62:5168-77
  31. Provinciali M, Re F, Donnini A, Orlando F, Bartozzi B, Di Stasio G, Smorlesi A. Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer 2005;115:36-45 https://doi.org/10.1002/ijc.20874
  32. Rarey M, Kramer B, Lengauer T, Klebe G. A fast flexible docking method using an incremental construction algorithm. J Mol Biol 1996;261:470-89 https://doi.org/10.1006/jmbi.1996.0477
  33. Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 2004; 428:198-202 https://doi.org/10.1038/nature02393
  34. Rich T, Harris J, Abrams R, Erickson B, Doherty M, Paradelo J, Small W Jr, Safran H, Wanebo HJ. Phase II study of external irradiation and weekly paclitaxel for nonmetastatic, unresectable pancreatic cancer: RTOG-98-12. Am J Clin Oncol 2004;27:51-6 https://doi.org/10.1097/01.coc.0000046300.88847.BF
  35. Roberti M, Pizzirani D, Simoni D, Rondanin R, Baruchello R, Bonora C, Buscemi F, Grimaudo S, Tolomeo M. Synthesis and Biological Evaluation of Resveratrol and Analogues as Apoptosis-Inducing Agents. J Med Chem 2003;46:3546-54 https://doi.org/10.1021/jm030785u
  36. Sanchez I, Dynlacht BD. New insights into cyclins, CDKs, and cell cycle control. Semin Cell Dev Biol 2005;16:311-21 https://doi.org/10.1016/j.semcdb.2005.02.007
  37. Tao W, South VJ, Zhang Y, Davide JP, Farrell L, Kohl NE, Sepp-Lorenzino L, Lobell RB. Induction of apoptosis by an inhibitor of the mitotic kinesin KSP requires both activation of the spindle assembly ckeckpoint and mitotic slippage. Cancer Cell 2005;8:49-59 https://doi.org/10.1016/j.ccr.2005.06.003
  38. Weaver BAA, Cleveland DW. Decoding the links between mitosis, cancer, and chemotherapy: the mitotic checkpoint, adaptation, and cell death. Cancer Cell 2005;8:7-12 https://doi.org/10.1016/j.ccr.2005.06.011
  39. Wei Y, Yu L, Bowen J, Gorovsky MA, Allis CD. Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 1999;97:99-109 https://doi.org/10.1016/S0092-8674(00)80718-7

Cited by

  1. The function of p27KIP1during tumor development vol.41, pp.11, 2009, https://doi.org/10.3858/emm.2009.41.11.102
  2. Resveratrol Protects Against Cisplatin-Induced Cardiotoxicity by Alleviating Oxidative Damage vol.24, pp.6, 2009, https://doi.org/10.1089/cbr.2009.0679
  3. Resveratrol, a Red Wine Polyphenol, Suppresses Pancreatic Cancer by Inhibiting Leukotriene A4Hydrolase vol.70, pp.23, 2009, https://doi.org/10.1158/0008-5472.can-10-2858
  4. MJ-29 Inhibits Tubulin Polymerization, Induces Mitotic Arrest, and Triggers Apoptosis via Cyclin-Dependent Kinase 1-Mediated Bcl-2 Phosphorylation in Human Leukemia U937 Cells vol.334, pp.2, 2009, https://doi.org/10.1124/jpet.109.165415
  5. MiR-196a Is Upregulated in Gastric Cancer and Promotes Cell Proliferation by Downregulating p27kip1 vol.11, pp.4, 2009, https://doi.org/10.1158/1535-7163.mct-11-1015
  6. miR-148b Functions as a Tumor Suppressor in Pancreatic Cancer by Targeting AMPKα1 vol.12, pp.1, 2013, https://doi.org/10.1158/1535-7163.mct-12-0534-t
  7. p27kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis vol.20, pp.3, 2015, https://doi.org/10.1007/s10495-014-1079-8
  8. Effect of resveratrol on cancer progression through the REG III expression pathway in head and neck cancer cells vol.49, pp.4, 2009, https://doi.org/10.3892/ijo.2016.3664
  9. The resveratrol analogue trimethoxystilbene inhibits cancer cell growth by inducing multipolar cell mitosis vol.56, pp.3, 2009, https://doi.org/10.1002/mc.22578
  10. Cancer Chemoprevention by Phytochemicals: Nature’s Healing Touch vol.22, pp.3, 2009, https://doi.org/10.3390/molecules22030395
  11. Combinational Proanthocyanidins and Resveratrol Synergistically Inhibit Human Breast Cancer Cells and Impact Epigenetic–Mediating Machinery vol.19, pp.8, 2009, https://doi.org/10.3390/ijms19082204
  12. Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in Cancer Prevention and Therapy vol.20, pp.18, 2009, https://doi.org/10.3390/ijms20184567
  13. mTOR pathway: A potential therapeutic target for spinal cord injury vol.145, pp.None, 2009, https://doi.org/10.1016/j.biopha.2021.112430