Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

• Published in: Prostate cancer and prostatic diseases Vol. 15; no. 3; pp. 260 - 264
• Main Authors: Chen, H-W, Chang, Y-F, Chuang, H-Y, Tai, W-T, Hwang, J-J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2012; Nature Publishing Group
• Subjects: 631/67/1059/602; 631/67/589/466; 631/92/436/2388; Animal models; Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer cells; Cancer Research; Carcinoma - diagnosis; Carcinoma - drug therapy; Carcinoma - metabolism; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cell survival; Disease Models, Animal; Drug therapy; Enzyme inhibitors; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - therapeutic use; Fatty Acid Synthases - antagonists & inhibitors; Fatty acids; Fatty-acid synthase; G1 Phase Cell Cycle Checkpoints - drug effects; Growth inhibition; Health aspects; Herpes simplex; Humans; In vivo methods and tests; Kinases; Male; Metabolism; Mice; Mice, Inbred NOD; Mice, SCID; Molecular Imaging; Molecular Targeted Therapy; original-article; Physiological aspects; Prostate cancer; Prostate carcinoma; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; siRNA; Thymidine; Thymidine kinase; Tumors; Viruses; Taiwan; C75; siFASN; molecular imaging; fatty acid synthase
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/pcan.2012.15

Background: Fatty acid synthase (FASN) is highly upregulated in human prostate carcinomas. Inhibition of FASN could arrest cell cycle and trigger apoptosis rapidly, implying the reliance of cancer cell survival on FASN. However, little is known about the effect of C75, a FASN inhibitor, and siFASN (that is, small interfering RNA targeted at FASN) on prostate cancer in living subjects. Methods: We used C75 and siFASN to mediate the endogenous fatty acid metabolism in LNCaP human prostate cancer cells stably expressing herpes simplex virus type 1 thymidine kinase ( HSV1-tk ) and luciferase ( luc ) reporter genes, and assessed the effect of FASN blockade with different schedules of administration on tumor growth using noninvasive molecular imaging. Results: FASN blockade exhibited the proliferative inhibition and induced G1-phase cell cycle arrest of LNCaP cells. For in vivo studies, the tumor growth inhibition by C75 (total 120 mg kg −1 ; 30 mg kg −1 once a week or 15 mg kg −1 twice a week for 4 weeks) and siFASN (1.4 mg kg −1 every alternate day up to 16 days) treatments were 80% and 70%, respectively, compared with that of the control. Conclusion: The results suggest that C75 may be superior to siFASN in anticancer effect on prostate cancer.