Furanoic Lipid F-6, A Novel Anti-Cancer Compound that Kills Cancer Cells by Suppressing Proliferation and Inducing Apoptosis
AbstractIdentifying novel anti-cancer drugs is important for devising better cancer treatment options. In a series of studies designed to identify novel therapeutic compounds, we recently showed that a C-20 fatty acid (12,15-epoxy-13,14-dimethyleicosa-12,14-dienoic acid, a furanoic acid or F-6) present in the lipid fraction of the secretions of the Arabian Gulf catfish skin (Arius bilineatus Val.; AGCS) robustly induces neutrophil extracellular trap formation. Here, we demonstrate that a lipid mix (Ft-3) extracted from AGCS and F-6, a component of Ft-3, dose dependently kill two cancer cell lines (leukemic K-562 and breast MDA MB-231). Pure F-6 is approximately 3.5 to 16 times more effective than Ft-3 in killing these cancer cells, respectively. Multiplex assays and network analyses show that F-6 promotes the activation of MAPKs such as Erk, JNK, and p38, and specifically suppresses JNK-mediated c-Jun activation necessary for AP-1-mediated cell survival pathways. In both cell lines, F-6 suppresses PI3K-Akt-mTOR pathway specific proteins, indicating that cell proliferation and Akt-mediated protection of mitochondrial stability are compromised by this treatment. Western blot analyses of cleaved caspase 3 (cCasp3) and poly ADP ribose polymerase (PARP) confirmed that F-6 dose-dependently induced apoptosis in both of these cell lines. In 14-day cell recovery experiments, cells treated with increasing doses of F-6 and Ft-3 fail to recover after subsequent drug washout. In summary, this study demonstrates that C-20 furanoic acid F-6, suppresses cancer cell proliferation and promotes apoptotic cell death in leukemic and breast cancer cells, and prevents cell recovery. Therefore, F-6 is a potential anti-cancer drug candidate. View Full-Text
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Al-Hassan, J.M.; Fang Liu, Y.; Khan, M.A.; Yang, P.; Guan, R.; Wen, X.-Y.; Afzal, M.; Oommen, S.; Paul, B.M.; Nair, D.; Palaniyar, N.; Pace-Asciak, C. Furanoic Lipid F-6, A Novel Anti-Cancer Compound that Kills Cancer Cells by Suppressing Proliferation and Inducing Apoptosis. Cancers 2019, 11, 960.
Al-Hassan JM, Fang Liu Y, Khan MA, Yang P, Guan R, Wen X-Y, Afzal M, Oommen S, Paul BM, Nair D, Palaniyar N, Pace-Asciak C. Furanoic Lipid F-6, A Novel Anti-Cancer Compound that Kills Cancer Cells by Suppressing Proliferation and Inducing Apoptosis. Cancers. 2019; 11(7):960.Chicago/Turabian Style
Al-Hassan, Jassim M.; Fang Liu, Yuan; Khan, Meraj A.; Yang, Peiying; Guan, Rui; Wen, Xiao-Yan; Afzal, Mohammad; Oommen, Sosamma; Paul, Bincy M.; Nair, Divya; Palaniyar, Nades; Pace-Asciak, Cecil. 2019. "Furanoic Lipid F-6, A Novel Anti-Cancer Compound that Kills Cancer Cells by Suppressing Proliferation and Inducing Apoptosis." Cancers 11, no. 7: 960.
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