Steroids with inhibitory activity against the prostate cancer cells and chemical diversity of marine alga Tydemania expeditionis

A new diketosteroid, (E)-stigmasta-24(28)-en-3,6-dione (1), along with three known steroids (2-4) was isolated from marine alga Tydemania expeditionis collected in China Sea. Their structures were elucidated by extensive spectroscopic methods. Comparison of the chemical constituents revealed significant diversity among different locations. The biological activities of 1, 3 and 4 were evaluated on the prostate cancer cell lines and androgen receptor. Compound 1 exhibited moderate inhibitory activities against the prostate cancer cells DU145, PC3 and LNCaP with IC50 values of 31.27 +/- 1.50. 40.59 +/- 3.10 and 19.80 +/- 3.84 mu M, respectively. Compound 3 showed more potent activities with IC50 values of 12.38 +/- 2.47, 2.14 +/- 0.33 and 1.38 +/- 0.07 mu M, respectively. However, compound 4 showed only weak inhibitory activities on LNCaP cells and was inactive on DU 145 and PC3 cells. A competitive binding assay showed that compound 1 exhibited significant affinity to the androgen receptor with an IC50 value of 7.19 +/- 0.45 mu M, while 3 and 4 were inactive. The fact that the inhibitory properties of 1 and 3 against the prostate cancer cells were inconsistent with their affinities to the androgen receptor suggested that there might be other mechanism of action involved in the cytotoxic activity. (C) 2012 Elsevier B.V. All rights reserved.