Biological activities of fusarochromanone: a potent anti-cancer agent

BMC Research Notes

John L Clifford³  Shile Huang⁴  Brian A Salvatore¹  Christopher G Kevil⁸  Yong-Yu Liu⁶  Quincy Quick⁵  Gopi K Kolluru⁸  Kaustubh N Bhinge⁶  Yang Wu⁴  Mansoureh Barzegar⁴  Ying Gu⁴  Yoon-Jee Kim⁴  Brian D Furmanski⁷  Tara Williams-Hart²  Steven Adelmund¹  Phillip Palyok¹  Elahe Mahdavian¹ 

[1] Department of Chemistry and Physics, LSU-Shreveport, One University Place, Shreveport, LA 71115, USA;Department of Biological Science, LSU-Shreveport, Shreveport, USA;US Army Institute of Surgical Research, Fort Sam, Houston, TX 78234, USA;Department of Biochemistry and Molecular Biology, LSUHSC-Shreveport, Shreveport, USA;Department of Biological Sciences, Tennessee State University, Nashville, USA;Department of Basic Pharmaceutical Sciences, University of Louisiana-Monroe, Monroe, USA;GlaxoSmithKline, Research Triangle, Park, NC, USA;Department of Pathology, LSUHSC-Shreveport, Shreveport, USA

关键词: Fusarochromanone;    Small bioactive molecule;    Anti-angiogenic;    Anti-cancer;    Pro-apoptotic;   

Others  :  1129899
DOI  :  10.1186/1756-0500-7-601

 received in 2013-10-27, accepted in 2014-08-15,  发布年份 2014

【 摘 要 】

Background

Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity.

Results

Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC₅₀ ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells.

Conclusions

Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101’s molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.

【 授权许可】

   
2014 Mahdavian et al.; licensee BioMed Central Ltd.

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