Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells

Chae,Jung-Il; Jeon,Young-Joo; Shim,Jung-Hyun

doi:10.3892/or.2013.2353

Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells

Authors:
- Jung-Il Chae
- Young-Joo Jeon
- Jung-Hyun Shim
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Affiliations: Department of Dental Pharmacology, School of Dentistry, Brain Korea 21 Project, Chonbuk National University, Jeonju 561‑756, Republic of Korea, College of Pharmacy, Mokpo National University, Muan, Jeonnam 534-729, Republic of Korea
Published online on: March 20, 2013 https://doi.org/10.3892/or.2013.2353
Pages: 2318-2324

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Abstract

Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer and is associated with a poor patient prognosis due to its rapid progression. Novel therapeutic agents such as honokiol (HNK) improve the clinical outcomes of cancer therapy, yet the mechanisms involved have not been fully elucidated. The present study examined the regulatory effects of HNK on the growth and apoptosis of MSTO-211H mesothelioma cells and investigated its anticancer mechanism. The results revealed that HNK significantly reduced the cell viability and increased the sub-G1 population in MSTO-211H cells and suppressed the expression of the specificity protein 1 protein (Sp1). HNK reduced the transcriptional activity of Sp1 regulatory proteins, including cyclin D1, Mcl-1 and survivin, and, thus, induced apoptosis signaling pathways by increasing Bax, reducing Bid and Bcl-xl and activating caspase-3 and PARP in mesothelioma cells. The results suggest that Sp1, a novel molecular target of HNK, may be related to cell cycle arrest and apoptosis induction through the modulation of signal transduction pathways in MPM.

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1	Cugell DW and Kamp DW: Asbestos and the pleura: a review. Chest. 125:1103–1117. 2004. View Article : Google Scholar
2	Tsao AS, Wistuba I, Roth JA and Kindler HL: Malignant pleural mesothelioma. J Clin Oncol. 27:2081–2090. 2009. View Article : Google Scholar : PubMed/NCBI
3	Broaddus VC: Asbestos, the mesothelial cell and malignancy: a matter of life or death. Am J Respir Cell Mol Biol. 17:657–659. 1997. View Article : Google Scholar : PubMed/NCBI
4	Morinaga K, Kishimoto T, Sakatani M, Akira M, Yokoyama K and Sera Y: Asbestos-related lung cancer and mesothelioma in Japan. Ind Health. 39:65–74. 2001. View Article : Google Scholar : PubMed/NCBI
5	Dufresne A, Begin R, Churg A and Masse S: Mineral fiber content of lungs in patients with mesothelioma seeking compensation in Quebec. Am J Respir Crit Care Med. 153:711–718. 1996. View Article : Google Scholar : PubMed/NCBI
6	Britton M: The epidemiology of mesothelioma. Semin Oncol. 29:18–25. 2002. View Article : Google Scholar : PubMed/NCBI
7	Zellos L and Sugarbaker DJ: Current surgical management of malignant pleural mesothelioma. Curr Oncol Rep. 4:354–360. 2002. View Article : Google Scholar : PubMed/NCBI
8	Gupta SC, Kim JH, Prasad S and Aggarwal BB: Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev. 29:405–434. 2010. View Article : Google Scholar : PubMed/NCBI
9	Liou KT, Shen YC, Chen CF, Tsao CM and Tsai SK: Honokiol protects rat brain from focal cerebral ischemia-reperfusion injury by inhibiting neutrophil infiltration and reactive oxygen species production. Brain Res. 992:159–166. 2003. View Article : Google Scholar
10	Bai X, Cerimele F, Ushio-Fukai M, et al: Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem. 278:35501–35507. 2003. View Article : Google Scholar : PubMed/NCBI
11	Chen F, Wang T, Wu YF, et al: Honokiol: a potent chemotherapy candidate for human colorectal carcinoma. World J Gastroenterol. 10:3459–3463. 2004.PubMed/NCBI
12	Wolf I, O’Kelly J, Wakimoto N, et al: Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest. Int J Oncol. 30:1529–1537. 2007.PubMed/NCBI
13	Sheu ML, Liu SH and Lan KH: Honokiol induces calpain-mediated glucose-regulated protein-94 cleavage and apoptosis in human gastric cancer cells and reduces tumor growth. PLoS One. 2:e10962007. View Article : Google Scholar : PubMed/NCBI
14	Ishitsuka K, Hideshima T, Hamasaki M, et al: Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis. Blood. 106:1794–1800. 2005. View Article : Google Scholar : PubMed/NCBI
15	Yang SE, Hsieh MT, Tsai TH and Hsu SL: Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem Pharmacol. 63:1641–1651. 2002. View Article : Google Scholar : PubMed/NCBI
16	Shigemura K, Arbiser JL, Sun SY, et al: Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer. 109:1279–1289. 2007. View Article : Google Scholar : PubMed/NCBI
17	Chu S and Ferro TJ: Sp1: regulation of gene expression by phosphorylation. Gene. 348:1–11. 2005. View Article : Google Scholar : PubMed/NCBI
18	Deniaud E, Baguet J, Mathieu AL, Pages G, Marvel J and Leverrier Y: Overexpression of Sp1 transcription factor induces apoptosis. Oncogene. 25:7096–7105. 2006. View Article : Google Scholar : PubMed/NCBI
19	Li L and Davie JR: The role of Sp1 and Sp3 in normal and cancer cell biology. Ann Anat. 192:275–283. 2010. View Article : Google Scholar : PubMed/NCBI
20	Sankpal UT, Goodison S, Abdelrahim M and Basha R: Targeting Sp1 transcription factors in prostate cancer therapy. Med Chem. 7:518–525. 2011. View Article : Google Scholar : PubMed/NCBI
21	Jutooru I, Chadalapaka G, Sreevalsan S, et al: Arsenic trioxide downregulates specificity protein (Sp) transcription factors and inhibits bladder cancer cell and tumor growth. Exp Cell Res. 316:2174–2188. 2010. View Article : Google Scholar
22	Mann J: Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer. 2:143–148. 2002. View Article : Google Scholar : PubMed/NCBI
23	Park EJ, Min HY, Chung HJ, et al: Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells. Cancer Lett. 277:133–140. 2009. View Article : Google Scholar : PubMed/NCBI
24	Wang T, Chen F, Chen Z, et al: Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. World J Gastroenterol. 10:2205–2208. 2004.PubMed/NCBI
25	Arora S, Bhardwaj A, Srivastava SK, et al: Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS One. 6:e215732011. View Article : Google Scholar : PubMed/NCBI
26	Ishikawa C, Arbiser JL and Mori N: Honokiol induces cell cycle arrest and apoptosis via inhibition of survival signals in adult T-cell leukemia. Biochim Biophys Acta. 1820:879–887. 2012. View Article : Google Scholar : PubMed/NCBI
27	Rajendran P, Li F, Shanmugam MK, et al: Honokiol inhibits signal transducer and activator of transcription-3 signaling, proliferation, and survival of hepatocellular carcinoma cells via the protein tyrosine phosphatase SHP-1. J Cell Physiol. 227:2184–2195. 2012. View Article : Google Scholar : PubMed/NCBI
28	Riss TL and Moravec RA: Use of multiple assay endpoints to investigate the effects of incubation time, dose of toxin, and plating density in cell-based cytotoxicity assays. Assay Drug Dev Technol. 2:51–62. 2004. View Article : Google Scholar : PubMed/NCBI
29	Li Y, Huang W, Huang S, Du J and Huang C: Screening of anti-cancer agent using zebrafish: comparison with the MTT assay. Biochem Biophys Res Commun. 422:85–90. 2012. View Article : Google Scholar : PubMed/NCBI
30	Chiefari E, Brunetti A, Arturi F, et al: Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation? BMC Cancer. 2:352002. View Article : Google Scholar : PubMed/NCBI
31	Hosoi Y, Watanabe T, Nakagawa K, et al: Up-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancer. Int J Oncol. 25:461–468. 2004.PubMed/NCBI
32	Wang L, Wei D, Huang S, et al: Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res. 9:6371–6380. 2003.PubMed/NCBI
33	Yao JC, Wang L, Wei D, et al: Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer. Clin Cancer Res. 10:4109–4117. 2004. View Article : Google Scholar
34	Zannetti A, Del Vecchio S, Carriero MV, et al: Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma. Cancer Res. 60:1546–1551. 2000.PubMed/NCBI
35	Davie JR, He S, Li L, et al: Nuclear organization and chromatin dynamics - Sp1, Sp3 and histone deacetylases. Adv Enzyme Regul. 48:189–208. 2008. View Article : Google Scholar : PubMed/NCBI
36	Lee KA, Lee YJ, Ban JO, et al: The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1. Int J Mol Med. 30:21–27. 2012.
37	Culver C, Melvin A, Mudie S and Rocha S: HIF-1α depletion results in SP1-mediated cell cycle disruption and alters the cellular response to chemotherapeutic drugs. Cell Cycle. 10:1249–1260. 2011.
38	Blume SW, Snyder RC, Ray R, Thomas S, Koller CA and Miller DM: Mithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo. J Clin Invest. 88:1613–1621. 1991. View Article : Google Scholar : PubMed/NCBI
39	Chintharlapalli S, Papineni S, Lei P, Pathi S and Safe S: Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors. BMC Cancer. 11:3712011. View Article : Google Scholar
40	Pietrzak M and Puzianowska-Kuznicka M: p53-dependent repression of the human MCL-1 gene encoding an anti-apoptotic member of the BCL-2 family: the role of Sp1 and of basic transcription factor binding sites in the MCL-1 promoter. Biol Chem. 389:383–393. 2008. View Article : Google Scholar : PubMed/NCBI
41	Tapias A, Ciudad CJ, Roninson IB and Noe V: Regulation of Sp1 by cell cycle-related proteins. Cell Cycle. 7:2856–2867. 2008. View Article : Google Scholar : PubMed/NCBI