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

• Published in: Cancers 2019-07, Vol.11 (7), p.960
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antitumor agents; Apoptosis; Breast cancer; c-Jun protein; Cancer; Candidates; Caspase-3; Catfish; Cell activation; Cell death; Cell growth; Cell proliferation; Cell survival; Drug dosages; Ethanol; Kinases; Leukemia; Leukocytes (neutrophilic); Lipids; Metastasis; Mitochondria; Penicillin; Pleural effusion; Poly(ADP-ribose) polymerase; Proteins; Ribose; Secretions; Skin; Sodium; TOR protein; Transcription factors; Tumor cell lines
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers11070960

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 ( ; 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.