IOX-101, a novel small molecule, reduces AML cell proliferation by Akt enzyme inhibition


  • Rajagopalan Prasanna Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha
  • Martin Raju Department of Microbiology and Parasitology, College of Medicine, King Khalid University, Abha
  • Hateem Aseeri Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha
  • Ismail M. Helal 1. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; 2. Plant Researches Department, Nuclear Research Center, Atomic Energy Authority, P. N. 13759, Egypt
  • Ashraf A Elbessoumy 1. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; 2. Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt


Akt, acute myeloid leukemia (AML), apoptosis, cell cycle, IOX-101


Cancer of the blood continues to be a major mortality factor globally. Arylidene compounds are well known for their anticancer effects. Here we describe the biological efficacy of IOX-101, a potential lead-compound of arylidene in acute myeloid leukemia (AML). Initially, molecular docking analysis was performed to check the binding efficacy of the compound with protein kinase B (Akt). The ability of the molecule to inhibit AML proliferation was assessed in THP-1 and Kasumi-6 cells by a standard MTT assay. Hoechst 333258/propidium iodide (PI) staining was carried out to analyze the nuclear damage. Flow cytometry was performed to check the apoptotic and cell cycle changes in THP-1 cells. The effect of IOX-101 on Akt phosphorylation was assessed by Western blot analysis. Molecular docking revealed interaction and binding of IOX-101 with the active site of Akt enzyme. The compound reduced proliferation of both AML cell lines in a dose-responsive way. Nuclear staining and cell cycle results revealed DNA damage by IOX-101 in THP-1 cells, and a significant increase in early and late phase apoptotic cells. A dose-dependent dephosphorylation of Akt (Ser 473) by IOX-101 was observed, which indicated allosteric inhibition of Akt by the compound. Our results showed that the DNA damage-mediated antiproliferative effect of IOX-101 in AML cells was mediated by Akt enzyme inhibition, and that this molecule possesses an effective chemotherapeutic potential against AML.

Received: September 22, 2017; Revised: November 1, 2017; Accepted: November 7, 2017; Published online: November 28, 2017

How to cite this article: Rajagopalan Prasanna, Raju M, Aseeri H, Helal IM, Elbessoumy AA. IOX-101, a novel small molecule, reduces AML cell proliferation by Akt enzyme inhibition. Arch Biol Sci. 2018;70(2):321-7.


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Prasanna R, Raju M, Aseeri H, Helal IM, Elbessoumy AA. IOX-101, a novel small molecule, reduces AML cell proliferation by Akt enzyme inhibition. Arch Biol Sci [Internet]. 2018May30 [cited 2022Sep.29];70(2):321-7. Available from: