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Article

BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L)

  • Authors:
    • Ji Hoon Jang
    • Yoon Chul Cho
    • Ki Ho Kim
    • Kyung Seop Lee
    • Jinho Lee
    • Dong Eun Kim
    • Jun-Soo Park
    • Byeong-Churl Jang
    • Shin Kim
    • Taeg Kyu Kwon
    • Jong-Wook Park
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, School of Medicine, Keimyung University, Daegu, Republic of Korea, Department of Urology, Dongguk University, College of Medicine, Gyeongju, Republic of Korea, Department of Chemistry, Keimyung University, Daegu, Republic of Korea, Chronic Disease Research Center, School of Medicine, Keimyung University, Daegu, Republic of Korea
  • Pages: 1680-1690
    |
    Published online on: July 4, 2014
       https://doi.org/10.3892/ijo.2014.2534
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Abstract

Previously, we reported the potential of a novel Cdk inhibitor, 2-[1,1'-biphenyl]-4-yl-N-[5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-1H-indazol-3-yl]acetamide (BAI) as a cancer chemotherapeutic agent. In this study, we investigated mechanisms by which BAI modulates FTI-mediated apoptosis in human renal carcinoma Caki cells. BAI synergizes with FTI to activate DEVDase, cleavage of poly ADP-ribose polymerase (PARP), and degradation of various anti-apoptotic proteins in Caki cells. BAI plus LB42708-induced apoptosis was inhibited by pretreatment with pan-caspase inhibitor, z-VAD-fmk, but not by overexpression of CrmA. The ROS scavenger, N-acetylcysteine (NAC) did not reduce BAI plus LB4270-induced apoptosis. Co-treatment of BAI and LB42708 reduced the mitochondrial membrane potential (MMP, ∆Ψm) in a time-dependent manner, and induced release of AIF and cytochrome c from mitochondria in Caki cells. Furthermore, BAL plus LB42708 induced downregulation of anti-apoptotic proteins [c-FLIP (L), c-FLIP (s), Bcl-2, XIAP, and Mcl-1 (L)]. Especially, we found that BAI plus LB42708-induced apoptosis was significantly attenuated by overexpression of Bcl-2 and partially blocked by overexpression of c-FLIP (L). Taken together, our results show that the activity of BAI plus LB42708 modulate multiple components in apoptotic response of human renal Caki cells, and indicate a potential as combinational therapeutic agents for preventing cancer such as renal carcinoma.
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Copy and paste a formatted citation
Spandidos Publications style
Jang JH, Cho YC, Kim KH, Lee KS, Lee J, Kim DE, Park J, Jang B, Kim S, Kwon TK, Kwon TK, et al: BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L). Int J Oncol 45: 1680-1690, 2014.
APA
Jang, J.H., Cho, Y.C., Kim, K.H., Lee, K.S., Lee, J., Kim, D.E. ... Park, J. (2014). BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L). International Journal of Oncology, 45, 1680-1690. https://doi.org/10.3892/ijo.2014.2534
MLA
Jang, J. H., Cho, Y. C., Kim, K. H., Lee, K. S., Lee, J., Kim, D. E., Park, J., Jang, B., Kim, S., Kwon, T. K., Park, J."BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L)". International Journal of Oncology 45.4 (2014): 1680-1690.
Chicago
Jang, J. H., Cho, Y. C., Kim, K. H., Lee, K. S., Lee, J., Kim, D. E., Park, J., Jang, B., Kim, S., Kwon, T. K., Park, J."BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L)". International Journal of Oncology 45, no. 4 (2014): 1680-1690. https://doi.org/10.3892/ijo.2014.2534
Copy and paste a formatted citation
x
Spandidos Publications style
Jang JH, Cho YC, Kim KH, Lee KS, Lee J, Kim DE, Park J, Jang B, Kim S, Kwon TK, Kwon TK, et al: BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L). Int J Oncol 45: 1680-1690, 2014.
APA
Jang, J.H., Cho, Y.C., Kim, K.H., Lee, K.S., Lee, J., Kim, D.E. ... Park, J. (2014). BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L). International Journal of Oncology, 45, 1680-1690. https://doi.org/10.3892/ijo.2014.2534
MLA
Jang, J. H., Cho, Y. C., Kim, K. H., Lee, K. S., Lee, J., Kim, D. E., Park, J., Jang, B., Kim, S., Kwon, T. K., Park, J."BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L)". International Journal of Oncology 45.4 (2014): 1680-1690.
Chicago
Jang, J. H., Cho, Y. C., Kim, K. H., Lee, K. S., Lee, J., Kim, D. E., Park, J., Jang, B., Kim, S., Kwon, T. K., Park, J."BAI, a novel Cdk inhibitor, enhances farnesyltransferase inhibitor LB42708-mediated apoptosis in renal carcinoma cells through the downregulation of Bcl-2 and c-FLIP (L)". International Journal of Oncology 45, no. 4 (2014): 1680-1690. https://doi.org/10.3892/ijo.2014.2534
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