Biomolecules & Therapeutics

  • 제23권5호
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  • Pages.428-433
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  • 2015
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Acetylshikonin Inhibits Human Pancreatic PANC-1 Cancer Cell Proliferation by Suppressing the NF-κB Activity

  • Cho, Seok-Cheol (Department of Food Science & Engineering, Seowon University) ;
  • Choi, Bu Young (Department of Pharmaceutical Science & Engineering, Seowon University)
  • 투고 : 2015.07.13
  • 심사 : 2015.08.07
  • 발행 : 2015.09.01
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초록

Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-${\kappa}B$ signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-${\kappa}B$ activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

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참고문헌

  1. Abdulla, M. and Gruber, P. (2000) Role of diet modification in cancer prevention. Biofactors 12, 45-51. https://doi.org/10.1002/biof.5520120108
  2. Bosetti, C., Bertuccio, P., Negri, E., La Vecchia, C., Zeegers, M. P. and Boffetta, P. (2012) Pancreatic cancer: overview of descriptive epidemiology. Mol. Carcinog. 51, 3-13. https://doi.org/10.1002/mc.20785
  3. Butler, A. M., Scotti Buzhardt, M. L., Erdogan, E., Li, S., Inman, K. S., Fields, A. P. and Murray, N. R. (2015) A small molecule inhibitor of atypical protein kinase C signaling inhibits pancreatic cancer cell transformed growth and invasion. Oncotarget 6, 15297-15310. https://doi.org/10.18632/oncotarget.3812
  4. Calonghi, N., Pagnotta, E., Parolin, C., Mangano, C., Bolognesi, M. L., Melchiorre, C. and Masotti, L. (2007) A new EGFR inhibitor induces apoptosis in colon cancer cells. Biochem. Biophys. Res. Commun. 354, 409-413. https://doi.org/10.1016/j.bbrc.2006.12.214
  5. Chien, W., Lee, D. H., Zheng, Y., Wuensche, P., Alvarez, R., Wen, D. L., Aribi, A. M., Thean, S. M., Doan, N. B., Said, J. W. and Koeffler, H. P. (2014) Growth inhibition of pancreatic cancer cells by histone deacetylase inhibitor belinostat through suppression of multiple pathways including HIF, NF${\kappa}B$B, and mTOR signaling in vitro and in vivo. Mol. Carcinog. 53, 722-735. https://doi.org/10.1002/mc.22024
  6. Duan, J., Friedman, J., Nottingham, L., Chen, Z., Ara, G. and Van Waes, C. (2007) Nuclear factor-kappaB p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101. Mol. Cancer Ther. 6, 37-50.
  7. El Fitori, J., Su, Y., Buchler, P., Ludwig, R., Giese, N. A., Buchler, M. W., Quentmeier, H., Hines, O. J., Herr, I. and Friess, H. (2007) PKC 412 small-molecule tyrosine kinase inhibitor: single-compound therapy for pancreatic cancer. Cancer 110, 1457-1468. https://doi.org/10.1002/cncr.22931
  8. Hsu, C. C., Lien, J. C., Chang, C. W., Chang, C. H., Kuo, S. C. and Huang, T. F. (2013) Yuwen02f1 suppresses LPS-induced endotoxemia and adjuvant-induced arthritis primarily through blockade of ROS formation, NF${\kappa}B$B and MAPK activation. Biochem. Pharmacol. 85, 385-395. https://doi.org/10.1016/j.bcp.2012.11.002
  9. Im, N. K., Jang, W. J., Jeong, C. H. and Jeong, G. S. (2014) Delphinidin suppresses PMA-induced MMP-9 expression by blocking the NF-kappaB activation through MAPK signaling pathways in MCF-7 human breast carcinoma cells. J. Med. Food 17, 855-861. https://doi.org/10.1089/jmf.2013.3077
  10. Lee, C. H., Jeon, Y. T., Kim, S. H. and Song, Y. S. (2007) NF-kappaB as a potential molecular target for cancer therapy. Biofactors 29, 19-35. https://doi.org/10.1002/biof.5520290103
  11. Liu, Y., Cao, W., Zhang, B., Liu, Y. Q., Wang, Z. Y., Wu, Y. P., Yu, X. J., Zhang, X. D., Ming, P. H., Zhou, G. B. and Huang, L. (2013) The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy. Sci. Rep. 3, 3098.
  12. Moon, J., Koh, S. S., Malilas, W., Cho, I. R., Kaewpiboon, C., Kaowinn, S., Lee, K., Jhun, B. H., Choi, Y. W. and Chung, Y. H. (2014) Acetylshikonin induces apoptosis of hepatitis B virus X proteinexpressing human hepatocellular carcinoma cells via endoplasmic reticulum stress. Eur. J. Pharmacol. 735, 132-140. https://doi.org/10.1016/j.ejphar.2014.04.021
  13. Moser, C., Schachtschneider, P., Lang, S. A., Gaumann, A., Mori, A., Zimmermann, J., Schlitt, H. J., Geissler, E. K. and Stoeltzing, O. (2008) Inhibition of insulin-like growth factor-I receptor (IGF-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis. Eur. J. Cancer 44, 1577-1586. https://doi.org/10.1016/j.ejca.2008.04.003
  14. Nishino, H., Tokuda, H., Murakoshi, M., Satomi, Y., Masuda, M., Onozuka, M., Yamaguchi, S., Takayasu, J., Tsuruta, J., Okuda, M., Khachik, F., Narisawa, T., Takasuka, N. and Yano, M. (2000) Cancer prevention by natural carotenoids. Biofactors 13, 89-94. https://doi.org/10.1002/biof.5520130115
  15. Pahl, H. L. (1999) Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18, 6853-6866. https://doi.org/10.1038/sj.onc.1203239
  16. Raimondi, S., Maisonneuve, P. and Lowenfels, A. B. (2009) Epidemiology of pancreatic cancer: an overview. Nat. Rev. Gastroenterol. Hepatol. 6, 699-708. https://doi.org/10.1038/nrgastro.2009.177
  17. Reddy, L., Odhav, B. and Bhoola, K. D. (2003) Natural products for cancer prevention: a global perspective. Pharmacol. Ther. 99, 1-13. https://doi.org/10.1016/S0163-7258(03)00042-1
  18. Tafani, M., Pucci, B., Russo, A., Schito, L., Pellegrini, L., Perrone, G. A., Villanova, L., Salvatori, L., Ravenna, L., Petrangeli, E. and Russo, M. A. (2013) Modulators of HIF1alpha and NFkB in cancer treatment: is it a rational approach for controlling malignant progression? Front. Pharmacol. 4, 13.
  19. Wiench, B., Eichhorn, T., Paulsen, M. and Efferth, T. (2012) Shikonin directly targets mitochondria and causes mitochondrial dysfunction in cancer cells. Evid. Based Complement. Alternat. Med. 2012, 726025.
  20. Zeng, Y., Liu, G. and Zhou, L. M. (2009) Inhibitory effect of acetylshikonin on human gastric carcinoma cell line SGC-7901 in vitro and in vivo. World J. Gastroenterol. 15, 1816-1820. https://doi.org/10.3748/wjg.15.1816

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