Open Access

Novel imidazo[1,2‑a]pyridine inhibits AKT/mTOR pathway and induces cell cycle arrest and apoptosis in melanoma and cervical cancer cells

  • Authors:
    • Saeb Aliwaini
    • Adel M. Awadallah
    • Rami Y. Morjan
    • Mariam Ghunaim
    • Hala Alqaddi
    • Asmaa Y. Abuhamad
    • Enas A. Awadallah
    • Yasmin M. Abughefra
  • View Affiliations

  • Published online on: May 13, 2019     https://doi.org/10.3892/ol.2019.10341
  • Pages: 830-837
  • Copyright: © Aliwaini et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the anti‑cancer activity of imidazo[1,2‑a]pyridine 5‑7 in the A375 and WM115 melanoma and HeLa cervical cancer cell lines. The viability of cancer cells was analyzed by the MTT assay. Apoptosis was quantified by flow cytometry following staining of the cells with AnnexinV/propidium iodide (PI). The cell cycle was evaluated by flow cytometry after staining of cells with PI. The three compounds inhibited the proliferation of all cells for half maximal inhibitory concentration ranging from 9.7 to 44.6 µM following 48‑h treatment. In addition, all cancer cells were more sensitive to compound 6 compared with the other compounds. Treatment with compound 6 induced G2/M cell cycle arrest and a significant increased level of intrinsic apoptosis in all tested cells. Furthermore, compound 6 reduced the levels of phospho (p)‑protein kinase B and p‑mechanistic target of rapamycin, and increased levels of the cell cycle inhibitors p53 and p21 and of the apoptosis‑associated proteins BCL2 associated X protein and active caspase‑9. Silencing p53 in A375 melanoma cells reduced compound 6‑induced apoptosis, which suggested that compound 6 may induce p53‑partially mediated apoptosis. These results demonstrated that imidazo[1,2‑a]pyridines 5‑7 are potential effective compounds in the treatment of melanoma and cervical cancers.
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July-2019
Volume 18 Issue 1

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

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Spandidos Publications style
Aliwaini S, Awadallah AM, Morjan RY, Ghunaim M, Alqaddi H, Abuhamad AY, Awadallah EA and Abughefra YM: Novel imidazo[1,2‑a]pyridine inhibits AKT/mTOR pathway and induces cell cycle arrest and apoptosis in melanoma and cervical cancer cells. Oncol Lett 18: 830-837, 2019
APA
Aliwaini, S., Awadallah, A.M., Morjan, R.Y., Ghunaim, M., Alqaddi, H., Abuhamad, A.Y. ... Abughefra, Y.M. (2019). Novel imidazo[1,2‑a]pyridine inhibits AKT/mTOR pathway and induces cell cycle arrest and apoptosis in melanoma and cervical cancer cells. Oncology Letters, 18, 830-837. https://doi.org/10.3892/ol.2019.10341
MLA
Aliwaini, S., Awadallah, A. M., Morjan, R. Y., Ghunaim, M., Alqaddi, H., Abuhamad, A. Y., Awadallah, E. A., Abughefra, Y. M."Novel imidazo[1,2‑a]pyridine inhibits AKT/mTOR pathway and induces cell cycle arrest and apoptosis in melanoma and cervical cancer cells". Oncology Letters 18.1 (2019): 830-837.
Chicago
Aliwaini, S., Awadallah, A. M., Morjan, R. Y., Ghunaim, M., Alqaddi, H., Abuhamad, A. Y., Awadallah, E. A., Abughefra, Y. M."Novel imidazo[1,2‑a]pyridine inhibits AKT/mTOR pathway and induces cell cycle arrest and apoptosis in melanoma and cervical cancer cells". Oncology Letters 18, no. 1 (2019): 830-837. https://doi.org/10.3892/ol.2019.10341