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 IC(50) values of 31.27±1.50, 40.59±3.10 and 19.80±3.84 µM, respectively. Compound 3 showed more potent activities with IC(50) values of 12.38±2.47, 2.14±0.33 and 1.38±0.07 µM, respectively. However, compound 4 showed only weak inhibitory activities on LNCaP cells and was inactive on DU145 and PC3 cells. A competitive binding assay showed that compound 1 exhibited significant affinity to the androgen receptor with an IC(50) value of 7.19±0.45 µM, 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.

Induction of differentiation and apoptosis in human promyelocytic leukemia HL60 cell line by a new type of steroids.

Mer-NF8054X is a new type of steroid whose structure has been established as 11-oxo-18, 22-cycloergosta-6, 8(14)-diene-3beta, 5beta, 9beta, 23S-tetraol (an 18, 22-cycloergostane), which has been reported to have antifungal activity against Aspergillus fumigatus. However, other biological activities are unknown. Herein, we reported that Mer-NF8054X inhibited cell growth of HL60 human leukemia cells, when used either singly or in combination with retinoic acid (RA). In addition, Mer-NF8054X alone induced differentiation and apoptosis of HL60 cells. The induction of differentiation of HL60 cells by Mer-NF8054X was synergistic in combination with RA. On the other hand, Emesterone A, an analogue of Mer-NF8054X which is missing a hydroxy residue from the third position, showed much lower activity than Mer-NF8054X on the inhibition of cell growth and the induction of cell differentiation and apoptosis. However, Emesterone B, an analogue of Emesterone A which is missing a hydroxy residue from the fifth position, showed higher activity than Emesterone A but lower activity than Mer-NF8054X when examined for the inhibition of cell growth and the induction of cell differentiation and apoptosis. These results suggested that Mer-NF8054X and its analogs may be a new type of differentiation inducing agent. The hydroxy residue at the third position or fifth position in Mer-NF8054X may be necessary, but not essential, for inhibition of growth and induction of both differentiation and apoptosis of HL60 cells. In addition, Mer-NF8054X enhanced the differentiation of HL60 cells induced by RA. Based on these results, Mer-NF8054X may have utility in the clinic in combination with RA for leukemia patients.

Hormonal therapy of endometriosis.

Hormonal therapy has long been the mainstay of the medical management of endometriosis. However, there is considerable confusion regarding the appropriate application of hormones in the treatment of endometriosis. This article critically reviews the current status of the steroidal therapy of endometriosis.

Potassium canrenoate in the treatment of long-term digoxin-induced arrhythmias in conscious dogs.

The effects of potassium canrenoate on arrhythmias induced by long-term progressive digoxin toxicity were studied in eight conscious beagle dogs. Sinus bradycardia and sinoatrial block, as well as atrioventricular (A-V) conduction disturbances, were consistently alleviated by administration of potassium canrenoate. Premature supraventricular (including junctional) and ventricular depolarizations as well as ventricular tachycardias were also suppressed. Although potassium canrenoate always terminated the digitalis-induced arrhythmias, it usually converted the rhythm to sinus arrhythmia rather than to normal sinus rhythm. Equimolar sodium canrenoate, but not potassium chloride, had similar reversal effects on arrhythmias induced by long-term digoxin intoxication. These data indicate that canrenoate, a diuretic agent with reported positive inotropic effects, may be useful in the treatment of digitalis-induced arrhythmias in man.