Open AccessFCY-302, a Novel Small Molecule, Induces Apoptosis in Leukemia and Myeloma Cells by Attenuating Key Antioxidant and Mitochondrial Enzymes
Author(s) -
Prasanna Rajagopalan,
Abdulrahim R. Hakami,
Mohammed Ragab,
Ashraf A. El-Bessoumy
Publication year - 2019
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504019x15555428221646
Subject(s) - apoptosis , jurkat cells , annexin , cancer cell , leukemia , cancer research , cell culture , multiple myeloma , mitochondrion , cancer , biology , medicine , biochemistry , microbiology and biotechnology , immunology , t cell , genetics , immune system
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 GI 50 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-G 0 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, Ca 2+ ATPase, and Mg 2+ 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.