Furanoic Lipid F-6, A Novel Anti-Cancer Compound that Kills Cancer Cells by Suppressing Proliferation and Inducing Apoptosis

• Main Authors: Jassim M. Al-Hassan, Yuan Fang Liu, Meraj A. Khan, Peiying Yang, Rui Guan, Xiao-Yan Wen, Mohammad Afzal, Sosamma Oommen, Bincy M. Paul, Divya Nair, Nades Palaniyar, Cecil Pace-Asciak
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Cancers
• Subjects: F-6 (furanoic F-acid); Gulf catfish lipids; cancer cell lines; cell proliferation; apoptosis; cell recovery
• Online Access: https://www.mdpi.com/2072-6694/11/7/960

Identifying 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 (<i>Arius bilineatus Val.</i>; 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.