Notch 1 signaling pathway is the potential target of novel anticancer drugs for the treatment of human nasopharyngeal cancer

Authors

  • Guo-Fang Guan Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130 041
  • De-Jun Zhang Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130 041
  • Ding Xin Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130 041
  • Lian-Ji Wen Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130 041
  • Duo-Jiao Yu Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130 041
  • Yan-Qing Lu Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130 041
  • Yan Zhao Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130 041
  • Tie-Jun Wang Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun 130 041

DOI:

https://doi.org/10.3329/bjp.v9i4.20342

Keywords:

Anticancer drug, Antiproliferative drug, Cancer, Stem cell, Verapamil

Abstract

Activation of Notch signaling pathway in cancer stem cells plays a crucial role in the regulation of selfrenewal and maintenance of side population cells.  In the present study, we have identified cancer stem like 2.7% side population cells from nasopharyngeal carcinoma samples whose prevalence was significantly reduced to 0.3% upon verapamil treatment. The protein level of Notch1 and Hes-1 are highly up-regulated in fluorescence-activated cell sorting purified side population cells and thus leads to the elevated expression of stem cell surface proteins (Oct-4, Sox2 and Nanog), which are essential for side population cells self-renewal. In addition, these nasopharyngeal carcinoma side population cells are CD133 and CD44 positive and they possess enhanced cell proliferation rate, highly tumorgenic and invasive. Our findings suggest that Notch1 signaling is a potential target of novel anticancer drugs, which could efficiently target and eradicate the cancer stem cells.

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References

Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: Cell fate control and signal integration in development. Science 1999; 284: 770-76.

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444: 756-60.

Chen JS, Pardo FS, Wang-Rodriguez J, Chu TS, Lopez JP, Aguilera J, Altuna X, Weisman RA, Ongkeko WM. EGFR regulates the side population in head and neck squamous cell carcinoma. Laryngoscope 2006; 116: 401-06.

Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, Nakauchi H, Taniguchi H. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 2006; 44: 240–51.

Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, Koh C, Zhang J, Li YM, Maciaczyk J, Nikkhah G, Dimeco F, Piccirillo S, Vescovi AL, Eberhart CG. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 2010; 28: 5-16.

Guo D, Xu BL, Zhang XH, Dong MM. Cancer stem-like side population cells in the human nasopharyngeal carcinoma cell line CNE-2 possess epithelial mesenchymal transition properties in association with metastasis. Oncol Rep. 2012; 28: 241-47.

Guo H, Li R, Zucker S, Toole BP. EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res. 2000; 60: 888-91.

Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF, Mori M. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 2006; 24: 506-13.

Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 2004; 101: 14228–33.

Ho MM, Ng AV, Lam S, Hung JY. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007; 15; 67: 4827-33.

Kawasaki BT, Hurt EM, Mistree T, Farrar WL. Targeting cancer stem cells with phytochemicals. Mol Interv. 2008; 8: 174-84.

Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA. 2004; 101: 781-86.

Lino MM, Merlo A, Boulay JL. Notch signaling in glioblas­toma: A developmental drug target. BMC Med. 2010; 8: 72.

Pannuti A, Foreman K, Rizzo P, Osipo C, Golde T, Osborne B, Miele L. Targeting Notch to target cancer stem cells. Clin Cancer Res. 2010; 16: 3141-3152.

Phillips TM, McBride WH, Pajonk F. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst. 2006; 98: 1777-85.

Robinson SN, Seina SM, Gohr JC, Kuszynski CA, Sharp JG. Evidence for a qualitative hierarchy within the Hoechst-33342 ’side population’ (SP) of murine bone marrow cells. Bone Marrow Transplant. 2005; 35: 807-18.

Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, Lipkin SM. NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res. 2010; 70: 1469-78.

Teng Y, Wang X, Wang Y, Ma D.Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells. Biochem Biophys Res Commun. 2010; 12; 392: 373-79.

Wang J, Guo LP, Chen LZ, Zeng YX and Lu SH. Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res. 2007; 67: 3716-24.

Wang M, Li JT, Zeng YX, Hou JH, Lin QQ. Expression and significance of Notch1, p21WAF1 and involucrin in nasopharyngeal carcinoma (In Chinese). Ai Zheng. 2005; 24: 1230-34.

Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM. WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci USA. 2007; 104: 618-23.

Yanamoto S, Kawasaki G, Yoshitomi I, Iwamoto T. Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of the tongue and its possibility as a potential target for tongue cancer gene therapy. Oral Oncol. 2007; 43: 869-77.

Yu S, Zhang R, Liu F, Hu H, Yu S, Wang H. Down-regulation of Notch signaling by a γ-secretase inhibitor enhances the radiosensitivity of nasopharyngeal carcinoma cells. Oncol Rep. 2011; 26: 1323-28.

Yu S, Zhang R, Liu F, Wang H, Wu J, Wang Y. Inhibi-tion suppresses nasopharyngeal carcinoma by depleting cancer stemlike side population cells. Oncol Rep. 2012; 28: 561-66.

Zhang XP, Zheng G, Zou L, Liu HL, Hou LH, Zhou P, Yin DD, Zheng QJ, Liang L, Zhang SZ, Feng L, Yao LB, Yang AG, Han H, Chen JY. Notch activation promotes cell proliferation and the formation of neural stem cell-like colonies in human glioma cells. Mol Cell Biochem. 2008; 307: 101-08.

Zhang Y, Peng J, Zhang H, Zhang H, Zhu Y, Wan L, Chen J, Chen X, Lin R, Li H, Mao X, Jin K. Notch1 signaling is activated in cells expressing embryonic stem cell proteins in human primary nasopharyngeal carcinoma. J Otolaryngol Head Neck Surg. 2010; 39: 157-66.

Zhen Y, Zhao S, Li Q, Li Y, Kawamoto K. Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas. Cancer Lett. 2010; 292: 64-72.

Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP. Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci USA. 2002; 99: 12339-44.

Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the sidepopulation phenotype. Nat Med. 2001; 7: 1028-34.

Published

2014-10-31

How to Cite

Guan, G.-F., D.-J. Zhang, D. Xin, L.-J. Wen, D.-J. Yu, Y.-Q. Lu, Y. Zhao, and T.-J. Wang. “Notch 1 Signaling Pathway Is the Potential Target of Novel Anticancer Drugs for the Treatment of Human Nasopharyngeal Cancer”. Bangladesh Journal of Pharmacology, vol. 9, no. 4, Oct. 2014, pp. 557-66, doi:10.3329/bjp.v9i4.20342.

Issue

Section

Research Articles