跳至主要内容

MINS, a Novel Naphthalimide-Polyamine Conjugate, Induced Apoptosis Depending on p53 Status in Human Colon Cancer Cells

Read full paper at:
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=50849#.VE3YfVfHRK0

Natural polyamine is an ideal antitumor drug carrier because of the great requirement difference between cancer cells and normal cells. Previous data demonstrated that many cytotoxic drugs conjugated with natural or synthetic polyamines have potent antitumor effects. Up to now, the antitumor mechanism of conjugates of naphthalimides with polyamine remains poorly understood in human colon cancer cells. The aim of this study is to evaluate the effect of MINS (a novel naph-thalimide-polyamine conjugate) and mechanism of MINS in human colon cancer cells. Mitochondrial toxicity, which was generated by ROS from mitochondria electron transport chain, might be a major factor in MINS-inducted apoptosis. Our data also demonstrated that MINS-mediated cell apoptosis depend on p53 status, for MINS induced Caco-2 cells (p53 null) only necrosis but not apoptosis. Furthermore, the apoptotic effect of MINS is stronger than that of Amonafide, the parent drug of MINS. Our data suggested that the MINS-mediated cell apoptosis depend on p53 in human colon cancer cells.
Cite this paper
Li, M. , Yang, T. , Dai, F. , Li, Q. , Zhang, Y. , Xie, S. and Wang, C. (2014) MINS, a Novel Naphthalimide-Polyamine Conjugate, Induced Apoptosis Depending on p53 Status in Human Colon Cancer Cells. Open Journal of Apoptosis, 3, 59-69. doi: 10.4236/ojapo.2014.34007
 

[1] Cantero-Munoz, P., Urién, M.A. and Ruano-Ravina, A. (2011) Efficacy and Safety of Intraoperative Radiotherapy in Colorectal Cancer: A Systematic Review. Cancer Letters, 306, 121-133.
http://dx.doi.org/10.1016/j.canlet.2011.02.020
[2] Nelson, S.M., Ferguson, L.R. and Denny, W.A. (2004) DNA and the Chromosome-Varied Targets for Chemotherapy. Cell Chromosome, 3, 2. http://dx.doi.org/10.1186/1475-9268-3-2
[3] Brana, M.F. and Ramos, A. (2001) Naphthalimides as Anticancer Agents: Synthesis and Biological Activity. Current Medicinal Chemistry-Anti-Cancer Agents, 1, 237-255.
http://dx.doi.org/10.2174/1568011013354624
[4] Nasizadeh, S., Myhre, L., Thiman, L., Alm, K., Oredsson, S. and Persson, L. (2005) Importance of Polyamines in Cell Cycle Kinetics as Studied in a Transgenic System. Experimental Cell Research, 308, 254-264. http://dx.doi.org/10.1016/j.yexcr.2005.04.027
[5] Basuroy, U.K. and Gerner, E.W. (2006) Emerging Concepts in Targeting the Polyamine Metabolic Pathway in Epithelial Cancer Chemoprevention and Chemotherapy. Journal of Biochemistry, 139, 27-33.
http://dx.doi.org/10.1093/jb/mvj022
[6] Tian, Z.Y., Ma, H.X., Xie, S.Q., Wang, X. and Zhao, J. (2008) Synthesis, DNA Binding and Topoisomerase Inhibition of Mononaphthalimide Homospermidine Derivatives. Chinese Chemical Letters, 19, 509-512. http://dx.doi.org/10.1016/j.cclet.2008.03.006
[7] Xie, S., Wang, J., Zhang, Y. and Wang, C. (2010) Antitumor Conjugates with Polyamine Vectors and Their Molecular Mechanisms. Expert Opinion on Drug Delivery, 7, 1049-1061.
http://dx.doi.org/10.1517/17425247.2010.504205
[8] Xie, S.Q., Li. Q., Zhang, Y.H., Wang, J.H., Mei, Z.H., Zhao, J. and Wang, C. (2011) NPC-16, a Novel Naphthalimide-Polyamine Conjugate, Induced Apoptosis and Autophagy in Human Hepatoma HepG2 Cells and Bel-7402 Cells. Apoptosis, 16, 27-34. http://dx.doi.org/10.1007/s10495-010-0537-1
[9] Wang, Y., Zhang, X., Zhao, J., Xie, S. and Wang, C. (2012) Nonhematotoxic Naphthalene Diimide Modified by Polyamine: Synthesis and Biological Evaluation. Journal of Medicinal Chemistry, 55, 3502-3512. http://dx.doi.org/10.1021/jm300168w
[10] Xie, S.Q., Wu, Y.L., Cheng, P.F., Wang, M.W., Liu, G.C., Ma, Y.F., Zhao, J. and Wang, C.J. (2007) A Novel Homospermidine Conjugate Inhibits Growth and Induces Apoptosis in Human Hepatoma Cells. Acta Pharmacologica Sinica, 28, 1827-1834. http://dx.doi.org/10.1111/j.1745-7254.2007.00639.x
[11] Brana, M.F., Cacho, M., García, M.A., de Pascual-Teresa, B., Ramos, A., Acero, N., Llinares, F., Munoz-Mingarro, D., Abradelo, C., Rey-Stolle, M.F. and Yuste, M. (2002) Synthesis, Antitumor Activity, Molecular Modeling and DNA Binding Properties of a New Series of Imidazonaphthalimides. Journal of Medicinal Chemistry, 45, 5813-5816. http://dx.doi.org/10.1021/jm020950q
[12] Tian, Z.Y., Xie, S.Q., Mei, Z.H., Zhao, J., Gao, W.Y. and Wang, C.J. (2009) Conjugation of Substituted Naphthalimides to Polyamines as Cytotoxic Agents Targeting the Akt/mTOR Signal Pathway. Organic Biomolecular Chemistry, 7, 4651-4660. http://dx.doi.org/10.1039/b912685f
[13] Tian, Z.Y., Xie, S.Q., Du, Y.W., Ma, Y.F., Zhao, J., Gao, W.Y. and Wang, C.J. (2009) Synthesis, Cytotoxicity and Apoptosis of Naphthalimide Polyamine Conjugates as Antitumor Agents. European Journal of Medicinal Chemistry, 44, 393-399. http://dx.doi.org/10.1016/j.ejmech.2008.02.044
[14] Xie, S.Q., Li, Q., Zhang, Y.H., Wang, J.H., Zhao, J. and Wang, C.J. (2010) NNINspm, Naphthalimide-Polyamine Conjugate, Induces Hepatoma HepG2 Cell Apoptosis via PI3K/Akt Pathways. Chinese Pharmacological Bulletin, 26,169-174.
[15] Wasilewski, M. and Scorrano, L. (2009) The Changing Shape of Mitochondrial Apoptosis. Trends in Endocrinology Metabolism, 20, 287-294. http://dx.doi.org/10.1016/j.tem.2009.03.007
[16] Circu, M.L. and Aw, T.Y. (2010) Reactive Oxygen Species, Cellular Redox Systems and Apoptosis. Free Radical Biology Medicine, 48, 749-762. http://dx.doi.org/10.1016/j.freeradbiomed.2009.12.022
[17] Shen, K., Sun, L., Zhang, H., Xu, Y., Qian, X., Lu, Y., Li, Q., Ni, L. and Liu, J. (2013) A ROS-Mediated Lysosomal-Mitochondrial Pathway Is Induced by a Novel Amonafide Analogue, 7c, in Human Hela Cervix Carcinoma Cells. Cancer Letters, 333, 229-238. http://dx.doi.org/10.1016/j.canlet.2013.01.038
[18] Yang, L., Zhao, J., Zhu, Y., Tian, Z. and Wang, C. (2011) Reactive Oxygen Species (ROS) Accumulation Induced by Mononaphthalimide-Spermidine Leads to Intrinsic and AIF-Mediated Apoptosis in Hela Cells. Oncology Reports, 25, 1099-1107. http://dx.doi.org/10.3892/or.2011.1173
[19] Gonmes, N.P. and Espinosa, J.M. (2010) Gene-Specific Repression of the p53 Target Gene PUMA via Intragenic CTCF-Cohesin Binding. Genes Development, 24, 1022-1034.
http://dx.doi.org/10.1101/gad.1881010
[20] Al-Hai, 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 Research, 40, 7739-7752. http://dx.doi.org/10.1093/nar/gks545                     eww141027lx

评论

此博客中的热门博文

Does Immigration Promote the Investment of the Monopolistic Firm?

In the present paper, we examine the effect of increasing uncertainty of immigrants’ growth on the optimal timing of investment of a firm that has a monopolistic power over the labor market. It is revealed that when the uncertainty of immigrants’ growth is more than a threshold level, increasing uncertainty of immigrants’ growth accelerates the optimal timing of firms’ investment and enhances the economic growth, even if the uncertainty of immigrants’ growth is formulated by the geometric Brownian motion, which is in sharp contrast to the standard result that an increase in the uncertainty postpones the optimal timing. With an increase in the immigrants over the past ten years, workforces in the host countries have been growing significantly to the extent that the immigrants represent 70% of the increase in the workforce in Europe, and 47% in the United States as OECD indicates. In the present paper, we attempted to investigate the effect of increased uncertainty caused by the growi...

Education Policy Implementation: A Mechanism for Enhancing Primary Education Development in Zanzibar

Education is one of the fundamental rights of individuals; therefore, the government of a country needs to develop and strengthen educational policy and quality as well as to ensure that everyone has equal access to basic education. The improvement of access and quality of education in the world is becoming as an essential factor in development, whereas the basic education (primary school), is acknowledged as a foundation of the higher educational development for every country. To fulfill this goal, governments introduce several policies and procedures; however, it requires some reforms and participation from the politician, policymakers, and other stakeholders to re-examine educational policy so that it can lead to multiplication and betterment of the reforms. Educational reforms actually focus on accountability. A positive educational development and reform is very challenging and needs more effort and strategy on how to use and utilize the resources effectively as such it can achie...