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

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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, GR, 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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Keywords: Antioxidant enzyme; Antiproliferative; Apoptosis; Arylidene; Leukemia; Mitochondrial enzyme; Myeloma

Document Type: Research Article

Affiliations: Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia

Publication date: August 8, 2019

This article was made available online on April 17, 2019 as a Fast Track article with title: "FCY-302, a novel small molecule, induces apoptosis in leukemia and myeloma cells by attenuating key anti-oxidant and mitochondrial enzymes".

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

    From Volume 23, Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics is Open Access under the terms of the Creative Commons CC BY-NC-ND license.

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