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

被引:11
作者
Al-Hassan, Jassim M. [1 ]
Liu, Yuan Fang [2 ]
Khan, Meraj A. [2 ]
Yang, Peiying [3 ]
Guan, Rui [4 ,5 ]
Wen, Xiao-Yan [4 ,5 ,6 ,7 ,8 ]
Afzal, Mohammad [1 ]
Oommen, Sosamma [9 ]
Paul, Bincy M. [1 ]
Nair, Divya [1 ]
Palaniyar, Nades [2 ,6 ,7 ,8 ]
Pace-Asciak, Cecil [2 ,10 ]
机构
[1] Kuwait Univ, Fac Sci, Dept Biol Sci, Safat 13060, Kuwait
[2] Hosp Sick Children, PGCRL, Program Translat Med, Toronto, ON M5G 0A4, Canada
[3] Univ Texas MD Anderson Canc Ctr, Dept Palliat Rehabil & Integrat Med, Houston, TX 77030 USA
[4] St Michaels Hosp, Unity Hlth Toronto, Zebrafish Ctr Adv Drug Discovery, Toronto, ON M5B 1W8, Canada
[5] St Michaels Hosp, Unity Hlth Toronto, Keenan Res Ctr Biomed Sci, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada
[6] Univ Toronto, Fac Med, Dept Lab Med, Toronto, ON M5G 0A4, Canada
[7] Univ Toronto, Fac Med, Dept Pathobiol, Toronto, ON M5G 0A4, Canada
[8] Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON M5G 0A4, Canada
[9] CMS Coll, Dept Zool, Kottayam 686001, Kerala, India
[10] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada
关键词
F-6 (furanoic F-acid); Gulf catfish lipids; cancer cell lines; cell proliferation; apoptosis; cell recovery; FATTY-ACIDS; BREAST-CANCER; CYTOTOXICITY; SKIN;
D O I
10.3390/cancers11070960
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (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.
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页数:17
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