Open Access

Effect of API‑1 and FR180204 on cell proliferation and apoptosis in human DLD‑1 and LoVo colorectal cancer cells

  • Authors:
    • Atiye Seda Yar Saglam
    • Ebru Alp
    • Zubeyir Elmazoglu
    • Emine Sevda Menevse
  • View Affiliations

  • Published online on: August 10, 2016     https://doi.org/10.3892/ol.2016.4995
  • Pages: 2463-2474
  • Copyright: © Saglam et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The activation of the phosphatidylinositol-3 kinase/v‑akt murine thymoma viral oncogene homolog (Akt) and mitogen activated protein kinase kinase/extracellular signal‑regulated kinase (ERK) pathways are implicated in the majority of cancers. Selective inhibition of Akt and ERK represents a potential approach for cancer therapy. Therefore, the present study aimed to investigate the apoptotic and anti‑proliferative effects of the novel and selective Akt inhibitor 4‑amino‑5,8‑di­hydro‑5‑oxo‑8-β-D-ribo­furan­osyl-pyrido[2,3-d]pyrimidine-6‑carboxamide (API‑1) and selective ERK1/2 inhibitor FR180204 (FR) alone and in combination on colorectal cancer (CRC) cells (DLD‑1 and LoVo). In addition, the effects of API‑1 and FR on Akt and ERK signaling pathways were also investigated. The effects of the agents on DLD‑1 and LoVo cells were evaluated in terms of cell viability, cytotoxicity, DNA synthesis rate, DNA fragmentation and caspase‑3 activity levels. In addition, quantitative reverse transcription‑polymerase chain reaction and western blot analysis were performed to examine relevant mRNA and protein levels. The present study observed that the combination of FR with API‑1 resulted in significant apoptosis and cytotoxicity compared with any single agent alone in a time‑dependent manner in these cells. Also, treatment with FR and API‑1 in combination decreased the expression levels of B‑cell lymphoma‑2 (BCL2), Bcl‑2‑like 1, cyclin D1 and cMYC, and increased the expression levels of BCL2‑associated X protein and BCL2 antagonist/killer via phosphorylated Akt and phosphorylated ERK1/2 downregulation. The combination of Akt and ERK1/2 inhibitors resulted in enhanced apoptotic and anti‑proliferative effects against CRC cells. The present study hypothesizes that the combination of FR and API‑1 in CRC cells may contribute toward potential anti‑carcinogenic effects. Additional analyses using other cancer cell lines and animal models are required to confirm these findings in vitro and in vivo.
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October-2016
Volume 12 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Saglam AS, Alp E, Elmazoglu Z and Menevse ES: Effect of API‑1 and FR180204 on cell proliferation and apoptosis in human DLD‑1 and LoVo colorectal cancer cells. Oncol Lett 12: 2463-2474, 2016
APA
Saglam, A.S., Alp, E., Elmazoglu, Z., & Menevse, E.S. (2016). Effect of API‑1 and FR180204 on cell proliferation and apoptosis in human DLD‑1 and LoVo colorectal cancer cells. Oncology Letters, 12, 2463-2474. https://doi.org/10.3892/ol.2016.4995
MLA
Saglam, A. S., Alp, E., Elmazoglu, Z., Menevse, E. S."Effect of API‑1 and FR180204 on cell proliferation and apoptosis in human DLD‑1 and LoVo colorectal cancer cells". Oncology Letters 12.4 (2016): 2463-2474.
Chicago
Saglam, A. S., Alp, E., Elmazoglu, Z., Menevse, E. S."Effect of API‑1 and FR180204 on cell proliferation and apoptosis in human DLD‑1 and LoVo colorectal cancer cells". Oncology Letters 12, no. 4 (2016): 2463-2474. https://doi.org/10.3892/ol.2016.4995