Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro

Cancer Cell International

Joseph Bryant¹  Ngeh J Toyang¹  Simone Badal²  Charah T Watson²  Henry I C Lowe¹ 

[1] Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA;Natural Products Institute, University of the West Indies, Mona, Jamaica

关键词: Ball moss;    Rostate cancer;    Kinase inhibition;    MRCKα kinase;    Cycloartane-3,24,25 triol;   

Others  :  794644
DOI  :  10.1186/1475-2867-12-46

 received in 2012-08-03, accepted in 2012-11-10,  发布年份 2012

【 摘 要 】

Background

Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation.

Methods

Kinase inhibition was investigated using competition binding (to the ATP sites) assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay.

Results

Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd₅₀ of 0.26 μM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC₅₀ values of 2.226 ± 0.28 μM and 1.67 ± 0.18 μM respectively.

Conclusions

These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer.

【 授权许可】

   
2012 Lowe et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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