Abstract B13: Cycloartane-3,24,25-triol: A cancer chemopreventive cycloartane inhibits MRCKα kinase and demonstrates anti prostate cancer activity in vitro

Abstract

Abstract In our study of the Jamaican ball moss (Tillandsia recurvata L.) for its prostate cancer chemotherapeutic properties, we have identified a number of cycloartane-type compounds from the chloroform crude extract. Cycloart-23-ene-3,25-diol was isolated and characterized from the extract. Attempts to run this compound in our kinase and antiproliferative assays were unsuccessful because of solubility problems. A search of the literature led us to Cycloartane-3,24,25-triol, a close analog of Cycloart-23-ene-3,25-diol. Cycloart-23-ene-3,25-diol differs from Cycloartane-3,24,25-triol only in the presence of a third hydroxyl group in this compound while Cycloart-23-ene-3,25-diol has only two hydroxyl groups. We isolated Cycloartane-3,24,25-triol from its source plant (Chrysanthemum morifolium) and screened it against a 451 kinase panel for inhibitory properties as well as for anti- prostate cancer cell proliferation activity using DU145 and PC-3 cell lines. Cycloartane-3,24,25-triol inhibited MRCKα (Myotonic dystrophy kinase-related Cdc42–binding kinase) kinase at a Kd of 0.26μM and showed IC50 values of 1.56±0.18μM and 2.04±0.28μM against DU145 and PC-3 prostate cancer cell lines respectively. MRCK kinases are now known to contribute to the process of tumor progression and metastasis through the control of the cytoskeleton which regulates tumor cell motility and invasion. In prostate cancer, the MRCKα kinase indirectly contributes to tumor progression by activating other kinases including the Lim kinase 1 (LIMK 1) which is over-expressed in prostate cancer and known to contribute to tumor cell invasion and migration leading to metastasis to other organs. This is the first report on the anti-prostate cancer activity and kinase inhibitory activity of Cycloartane-3,24,25-triol. The combined kinase and in vitro antiproliferation activity of Cycloartane-3,24,25-triol makes it a good candidate for further studies to determine its in vivo efficacy against prostate cancer. Citation Format: Henry I.C. Lowe, Ngeh J. Toyang, Joseph Bryant. Cycloartane-3,24,25-triol: A cancer chemopreventive cycloartane inhibits MRCKα kinase and demonstrates anti prostate cancer activity in vitro [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B13.