The online version of this article (doi:10.1186/1475-2867-12-46) contains supplementary material, which is available to authorized users.
The authors declare no competing interest at this time.
Conceived and designed the experiments: HL and JB, Acquisition of data: CW and NT, Analyzed and interpreted the data: NT and SB. Wrote the paper: SB and NT, Critical and intellectual revision of the article contents: SB and NT. All authors read and approved the final manuscript.
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.
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.
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.
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.
Lowe H: Anti-Tumor and Anti-Inflammatory Extracts of Plant Biomass and Their Uses. 2010, Jamaica, 1-14. US 7,713,556 B2
Cabrera GM, Seldes AM: Hydroperoxycycloartanes from Til landsia recurvata. J Nat Prod. 1995, 58: 1920-1924. CrossRef
Hall A: Rho GTPases and the actin cytoskeleton. Science. 1998, 23: 509-514. CrossRef
Heikkila T, Wheatley E, Crghton D, Schroder E, Boakes A, Kaye S, Mezna M, Pang L, Rushbrooke M, Turnbull A: Co-crystal structures of inhibitors with MRCKβ, a key regulator of tumor cell invasion. PloSOne. 2011, 6: 1-12. CrossRef
Jaffe A, Hall A: RHO GTPASES: biochemistry and biology. Annu Rev Cell Dev Bi. 2005, 21: 247-269. CrossRef
Benitaha SA, Valeróna PF, Aelstb L, Marshallc CJ, Lacala JC: Rho GTPases in human cancer: an unresolved link to upstream and downstream transcriptional regulation. Biochimica et Biophysica Acta. 2005, 1705: 121-132.
Terracciano D, Mazzarella C, Di Carlo A, Mariano A, Ferro M, Di Lorenzo G, Giordano A, Altieri V, De Placido S, Macchia V: Effects of the ErbB1/ErbB2 kinase inhibitor GW2974 on androgen-independent prostate cancer PC-3 cell line growth and NSE, chromogranin A and osteopontin content. Oncol Rep 2010. 2010, 24: 213-217.
Ngamwongsatit P, Banada PP, Panbangred W, Bhunia AK: WST-1-based cell cytotoxicity assay as a substitute for MTT-based assay for rapid detection of toxigenic Bacillus species using CHO cell line. J Microbiol Meth. 2008, 73: 211-215. CrossRef
- Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro
Henry I C Lowe
Charah T Watson
Ngeh J Toyang
- BioMed Central
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