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Article

Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer

  • Authors:
    • Sang-Won Hong
    • Kyung Hee Jung
    • Myung-Joo Choi
    • Da Young Kim
    • Hee‑Seung Lee
    • Hong-Mei Zheng
    • Guang Yong Li
    • Ibrahim  M. El‑Deeb
    • Byung Sun Park
    • So Ha Lee
    • Soon-Sun Hong
  • View Affiliations / Copyright

    Affiliations: NCEED and Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 400-712, Republic of Korea, Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 130-650, Republic of Korea
  • Pages: 1715-1722
    |
    Published online on: August 27, 2012
       https://doi.org/10.3892/ijo.2012.1609
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Abstract

The anticancer effect of a new pyrazole derivative, KI-10F (2-(4-(2-(4-(dimethylamino) phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol‑1-yl) acetonitrile)•3.5HCl) was evaluated in human colon cancer cells. KI-10F strongly suppressed the growth of human colon cancer cells and induced apoptosis by increasing the proportion of sub-G1 presenting apoptotic cells as well as causing cell cycle arrest at the G2/M phase. Apoptosis by KI-10F was confirmed by observation of an increase in the expression of cleaved caspase-3, caspase-8, caspase-9 and Bax, and the decrease of Bcl-2. Decreased expression of HIF-1α and VEGF, and the inhibition of HUVEC tube formation and migration showed that KI-10F effectively inhibited the angiogenesis process. Furthermore, in vivo study in a mouse xenograft model showed that KI-10F produced a stronger antitumor activity than 5-FU, a conventional anticancer drug prescribed for the treatment of colon cancer. The effects of KI-10F on tumor proliferation (PCNA), angiogenesis (CD34) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry using isolated tumor tissue samples. Taken together, our results demonstrated that KI-10F induces apoptosis and inhibits cell growth and angiogenesis both in vitro and in vivo. We suggest that KI-10F is an effective chemotherapeutic candidate for use against colon cancer.
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1. 

Shen W, Wang CY, Wang XH and Fu ZX: Oncolytic adenovirus mediated Survivin knockdown by RNA interference suppresses human colorectal carcinoma growth in vitro and in vivo. J Exp Clin Cancer Res. 28:812009. View Article : Google Scholar : PubMed/NCBI

2. 

Potter JD: Colorectal cancer: molecules and populations. J Natl Cancer Inst. 91:916–932. 1999. View Article : Google Scholar : PubMed/NCBI

3. 

Oh BY, Lee RA and Kim KH: siRNA targeting Livin decreases tumor in a xenograft model for colon cancer. World J Gastroenterol. 17:2563–2571. 2011. View Article : Google Scholar : PubMed/NCBI

4. 

Zhang N, Yin Y, Xu SJ and Chen WS: 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules. 13:1551–1569. 2008. View Article : Google Scholar : PubMed/NCBI

5. 

Pullarkat ST, Stoehlmacher J, Ghaderi V, Xiong YP, Ingles SA, Sherrod A, Warren R, Tsao-Wei D, Groshen S and Lenz HJ: Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J. 1:65–70. 2001. View Article : Google Scholar : PubMed/NCBI

6. 

Manfredini S, Bazzanini R, Baraldi PG, Bonora M, Marangoni M, Simoni D, Pani A, Scintu F, Pinna E and Pisano L: Pyrazole-related nucleosides. 4. Synthesis and antitumor activity of some 1-tetrahydropyranyl-4-substituted pyrazoles. Anticancer Drug Des. 11:193–204. 1996.PubMed/NCBI

7. 

Park HJ, Lee K, Park SJ, Ahn B, Lee JC, Cho H and Lee KI: Identification of antitumor activity of pyrazole oxime ethers. Bioorg Med Chem Lett. 15:3307–3312. 2005. View Article : Google Scholar : PubMed/NCBI

8. 

Lv PC, Li HQ, Sun J, Zhou Y and Zhu HL: Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents. Bioorg Med Chem. 18:4606–4614. 2010. View Article : Google Scholar : PubMed/NCBI

9. 

Bandgar BP, Totre JV, Gawande SS, Khobragade CN, Warangkar SC and Kadam PD: Synthesis of novel 3,5-diaryl pyrazole derivatives using combinatorial chemistry as inhibitors of tyrosinase as well as potent anticancer, anti-inflammatory agents. Bioorg Med Chem. 18:6149–6155. 2010. View Article : Google Scholar

10. 

Christodoulou MS, Liekens S, Kasiotis KM and Haroutounian SA: Novel pyrazole derivatives: synthesis and evaluation of anti-angiogenic activity. Bioorg Med Chem. 18:4338–4350. 2010. View Article : Google Scholar : PubMed/NCBI

11. 

Fan C, Su H, Zhao J, Zhao B, Zhang S and Miao J: A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin beta4 in H322 lung carcinoma cells. Eur J Med Chem. 45:1438–1446. 2010. View Article : Google Scholar : PubMed/NCBI

12. 

Calhelha RC, Ferreira IC, Peixoto D, Abreu RM, Vale-Silva LA, Pinto E, Lima RT, Alvelos MI, Vasconcelos MH and Queiroz MJ: Aminodi(hetero)arylamines in the thieno[3,2-b] pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells. Molecules. 17:3834–3843. 2010.

13. 

Pracharova J, Zerzankova L, Stepankova J, Novakova O, Farrer NJ, Sadler PJ, Brabec V and Kasparkova J: Interactions of DNA with a new platinum(IV) azide dipyridine complex activated by UVA and visible light: relationship to toxicity in tumor cells. Chem Res Toxicol. 25:1099–1111. 2010. View Article : Google Scholar : PubMed/NCBI

14. 

Weidner N, Semple JP, Welch WR and Folkman J: Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med. 324:1–8. 1991. View Article : Google Scholar : PubMed/NCBI

15. 

Cristi E, Perrone G, Toscano G, Verzi A, Nori S, Santini D, Tonini G, Vetrani A, Fabiano A and Rabitti C: Tumour proliferation, angiogenesis, and ploidy status in human colon cancer. J Clin Pathol. 58:1170–1174. 2005. View Article : Google Scholar : PubMed/NCBI

16. 

Chen JM, Li WH, Wang JD, Feng YD, Wu JH and Gong JP: Cell balance between apoptosis and proliferation in colon cancer and its correlation with prognosis. Ai Zheng. 24:554–558. 2005.(In Chinese).

17. 

Esposito E and Cuzzocrea S: New therapeutic strategy for Parkinson’s and Alzheimer’s disease. Curr Med Chem. 17:2764–2774. 2010.

18. 

El-Deeb IM and Lee SH: Design and synthesis of new potent anticancer pyrazoles with high FLT3 kinase inhibitory selectivity. Bioorg Med Chem. 18:3961–3973. 2010. View Article : Google Scholar : PubMed/NCBI

19. 

Schmitz I, Kirchhoff S and Krammer PH: Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol. 32:1123–1136. 2000. View Article : Google Scholar : PubMed/NCBI

20. 

Igney FH and Krammer PH: Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2:277–288. 2002. View Article : Google Scholar : PubMed/NCBI

21. 

Soengas MS, Capodieci P, Polsky D, Mora J, Esteller M, Opitz-Araya X, McCombie R, Herman JG, Gerald WL and Lazebnik YA: Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature. 409:207–211. 2001. View Article : Google Scholar : PubMed/NCBI

22. 

Nagane M, Levitzki A, Gazit A, Cavenee WK and Huang HJ: Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc Natl Acad Sci USA. 95:5724–5729. 1998. View Article : Google Scholar

23. 

Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW and Baldwin DT: Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 396:699–703. 1998. View Article : Google Scholar : PubMed/NCBI

24. 

Xu X, Zhang Y, Qu D, Jiang T and Li S: Osthole induces G2/M arrest and apoptosis in lung cancer A549 cells by modulating PI3K/Akt pathway. J Exp Clin Cancer Res. 30:332011. View Article : Google Scholar : PubMed/NCBI

25. 

Yang CJ, Wang CS, Hung JY, Huang HW, Chia YC, Wang PH, Weng CF and Huang MS: Pyrogallol induces G2-M arrest in human lung cancer cells and inhibits tumor growth in an animal model. Lung Cancer. 66:162–168. 2009. View Article : Google Scholar : PubMed/NCBI

26. 

Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R and Maxwell P: Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 394:485–490. 1998. View Article : Google Scholar : PubMed/NCBI

27. 

Bolat F, Haberal N, Tunali N, Aslan E, Bal N and Tuncer I: Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1alpha), and transforming growth factors beta1 (TGFbeta1) and beta3 (TGFbeta3) in gestational trophoblastic disease. Pathol Res Pract. 206:19–23. 2010. View Article : Google Scholar

28. 

Spano D and Zollo M: Tumor microenvironment: a main actor in the metastasis process. Clin Exp Metastasis. 29:381–395. 2012. View Article : Google Scholar : PubMed/NCBI

29. 

Tao BB, Zhang CC, Liu SY and Zhu YC: Involvement of HIF-1 in the migration-promoting effects of hydrogen sulfide in vascular endothelial cells under normoxic conditions. Sheng Li Xue Bao. 64:129–134. 2012.(In Chinese).

30. 

Ergun S, Kilic N, Wurmbach JH, Ebrahimnejad A, Fernando M, Sevinc S, Kilic E, Chalajour F, Fiedler W and Lauke H: Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes. Angiogenesis. 4:193–206. 2001. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Hong S, Jung KH, Choi M, Kim DY, Lee HS, Zheng H, Li GY, El‑Deeb IM, Park BS, Lee S , Lee S , et al: Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer. Int J Oncol 41: 1715-1722, 2012.
APA
Hong, S., Jung, K.H., Choi, M., Kim, D.Y., Lee, H., Zheng, H. ... Hong, S. (2012). Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer. International Journal of Oncology, 41, 1715-1722. https://doi.org/10.3892/ijo.2012.1609
MLA
Hong, S., Jung, K. H., Choi, M., Kim, D. Y., Lee, H., Zheng, H., Li, G. Y., El‑Deeb, I. M., Park, B. S., Lee, S. ., Hong, S."Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer". International Journal of Oncology 41.5 (2012): 1715-1722.
Chicago
Hong, S., Jung, K. H., Choi, M., Kim, D. Y., Lee, H., Zheng, H., Li, G. Y., El‑Deeb, I. M., Park, B. S., Lee, S. ., Hong, S."Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer". International Journal of Oncology 41, no. 5 (2012): 1715-1722. https://doi.org/10.3892/ijo.2012.1609
Copy and paste a formatted citation
x
Spandidos Publications style
Hong S, Jung KH, Choi M, Kim DY, Lee HS, Zheng H, Li GY, El‑Deeb IM, Park BS, Lee S , Lee S , et al: Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer. Int J Oncol 41: 1715-1722, 2012.
APA
Hong, S., Jung, K.H., Choi, M., Kim, D.Y., Lee, H., Zheng, H. ... Hong, S. (2012). Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer. International Journal of Oncology, 41, 1715-1722. https://doi.org/10.3892/ijo.2012.1609
MLA
Hong, S., Jung, K. H., Choi, M., Kim, D. Y., Lee, H., Zheng, H., Li, G. Y., El‑Deeb, I. M., Park, B. S., Lee, S. ., Hong, S."Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer". International Journal of Oncology 41.5 (2012): 1715-1722.
Chicago
Hong, S., Jung, K. H., Choi, M., Kim, D. Y., Lee, H., Zheng, H., Li, G. Y., El‑Deeb, I. M., Park, B. S., Lee, S. ., Hong, S."Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer". International Journal of Oncology 41, no. 5 (2012): 1715-1722. https://doi.org/10.3892/ijo.2012.1609
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