Open Access

ARTICLE

FCY-302, a Novel Small Molecule, Induces Apoptosis in Leukemia and Myeloma Cells by Attenuating Key Antioxidant and Mitochondrial Enzymes

Prasanna Rajagopalan^*†, Abdulrahim Hakami^*†, Mohammed Ragab^*, Ashraf Elbessoumy^*‡

* Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia
† Central Research Laboratory, College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia
‡ Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt

Oncology Research 2019, 27(8), 957-964. https://doi.org/10.3727/096504019X15555428221646

Abstract

Arylidene analogs are well proven for biological activities. FCY-302, a novel small molecule belonging to this class, was screened for its biological efficacy in leukemia and myeloma cells. FCY-302 selectively inhibited proliferation of cancer cells with GI50 values of 395.2 nM, 514.6 Nm, and 642.4 nM in HL-60, Jurkat, and RPMI-8226 cells, respectively. The compound also increased sub-G0 peak in the cancer cell cycle and favored apoptosis determined by annexin V assay. The compound decreased the antiapoptotic Bcl-2 levels and increased proapoptotic Bax proteins in leukemia and myeloma cell lines. FCY-302 attenuated the mitochondrial membrane-bound Na⁺ /K⁺ ATPase, Ca²⁺ ATPase, and Mg²⁺ ATPase enzyme activities and significantly decreased activities of antioxidant enzymes like SOD, CAT, G_R, and GST in all the three cancer cells tested. Our findings suggest that FCY-302 inhibits the proliferation of leukemia and myeloma cancer cells by altering key mitochondrial and antioxidant enzymes, eventually driving them to apoptosis. These results drive focus on FCY-302 and its analogs to be developed as potential small molecules with bioactivities against cancer.

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