stigmasterol and Prostatic-Neoplasms

Two new stigmastane-type steroids, stigmasta-5,22E-diene-3β,11α-diol (1) and stigmasta-5,22E-diene-3β,7α,11α-triol (2), together with eight known compounds, were isolated from the resinous exudates of Commiphora mukul. Their structures were established by extensive analysis of their HR-MS, 1D- and 2D-NMR (COSY, HMQC, HMBC and NOESY) spectra. The isolates were evaluated for their antiproliferative activities against four human cancer cell lines. Compound 2 demonstrated inhibitory effects with IC(50) values of 5.21, 9.04, 10.94 and 16.56 μM, respectively, against K562, MCF-7, PC3 and DU145 human cancer cell lines. Further study showed that 2 was able to enforce the PC3 cell cycle arrest in the G2/M phase, and induce the apoptosis of PC3 cells by activation of Bax, caspases 3 and 9, and by inhibition of Bcl-2. It was also found that 1 inhibited proliferation of PC3 cells via G0/G1 phase arrest of the cell cycle.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Commiphora; Humans; Male; Models, Molecular; Molecular Structure; Prostatic Neoplasms; Steroids; Structure-Activity Relationship

Saw Palmetto Berry Extract (SPBE) is applied for prostate health and treatment of urinary tract infections, nonbacterial prostitis and Benign Prostatic Hyperplasia (BPH) in man. An assumption is that SPBE affects tumor cell progression and migration in breast and prostate tissue. In this work, DU-145 cells were used to demonstrate that SPBE and its sterol components, beta-sitosterol and stigmasterol, inhibit prostate cancer growth by increasing p53 protein expression and also inhibit carcinoma development by decreasing p21 and p27 protein expression. In the presence of cholesterol, these features are not only reversed but increased significantly. The results show for the first time the potential of SPBE, beta-sitosterol and stigmasterol as potential anti-tumor agents. Since the protein p53 is also regarded as nuclear matrix protein facilitating actin cytoskeletal binding, 2D tractions were measured. The cell adhesion strength in the presence of SPBE, beta-sitosterol and cholesterol and the observation was that the increase in p53 expression triggered an increase in the intracellular force generation. The results suggest a dual function of p53 in cells.

Topics: Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Humans; Male; Plant Extracts; Prostatic Neoplasms; Serenoa; Sitosterols; Stigmasterol

In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.

Topics: Anticarcinogenic Agents; Case-Control Studies; Cholesterol; Databases, Factual; Diet Records; Estrogens, Non-Steroidal; Genistein; Humans; Isoflavones; Male; Middle Aged; Multivariate Analysis; Nutrition Assessment; Phytoestrogens; Phytosterols; Plant Preparations; Prostatic Neoplasms; Risk Factors; Stigmasterol; Surveys and Questionnaires; Texas