Enzymatic conversion of dihydrotestosterone from 3-keto to 3-enol form in the rat prostate

Dihydrotestosterone (DHT) is the active androgen, as well as a strong tumor promoter in the prostate, where several enzymes are essential for the regulation of its activity. We localized four enzymes promoting the enolization of the 3-keto group of DHT in rat prostate. The enzymes were purified by ion-exchange chromatography, acetone fractionation and gel filtration to homogeneity, and found to have molecular sizes of 19.5, 22.0, 44.5 and 21.5 kDa. A partial characterization of the four enzymes revealed that their structure consisted of a common chain of 14.5 kDa with various subunits which differentiate the four enzymes from each other. All the enzymes exerted their activity only on 5-dihydro 3-keto steroids. The total enzymatic activity was strongly influenced by animal age, being very low before sexual maturation, as well as after castration. In the latter case the level of total activity fell to about 8% of control animals. Activity was also estimated in human, pork, ram and bovine prostate and it was found that all these species have 20 - 25 times lower enzyme levels than rat. These results, in combination with the practically exclusive localization of the enzymes in the prostate, suggest a role relating to the bioavailability of DHT in this gland

Albumin possesses intrinsic enolase activity towards dihydrotestosterone which can differentiate benign from malignant breast tumors

Serum albumin was found to possess enolase activity towards the dihydrotestesterone (DHT) molecule, converting it from its 3-keto to 3-enol form. This activity was accompanied by albumin during all stages of purification, as well as following various treatments, a fact indicating that the enzymatic activity was an intrinsic property of albumin molecule and did not represent an impurity of the preparation. Enolase activity was decreased in parallel with the quantity of intact albumin molecules when proteolytic enzymes were used for their degradation. The activity was strongly inhibited by Ni (II) and Cu (II) ions, which bind to 3-histidine of the albumin molecule, as well as by oleic acid and cholesterol. It was also inhibited, in a reversible mantle, by surface - active agents. Enolase activity was found in all mammalian,species studied the specific activity however was very low in the se, nm of dogs. The administration of DHT to mice did not influence the albumin or enolase levels in their serum. The optimum pH of enolase was at 9.2, with a carbonate buffer solution. In addition to the serum, enolase activity was found to be a feature of intracellular, albumin. The two albumins exhibited the same specific activity and the same Km for DHT. The study of cytosolic albumin, obtained from human mammary gland tissue, revealed that benign and malignant tumors of this gland differed substantially with respect to their percentage of albumin. Significant differences were also observed in enolase activity, a consequence of the existence of a fraction of albumin in the malignant tissue in a polymeric form. This form exhibited a decreased enzymatic activity, compared to its monomeric form, exclusively encountered in benign breast specimens. The last observation, along with the quantitative reliable differentiation between benign and malignant breast tumors

Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells

A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC50 values of 121-230μg/ml (MCF-7), 121-184μg/ml (MDA-MD-23), 175-309μg/ml (HT29), 159-314μg/ml (K1), 180-225μg/ml (786-0) and 134->400μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells. © 2014 Elsevier Ireland Ltd

Current therapies in alleviating liver disorders and cancers with a special focus on the potential of vitamin D

Abstract Background Liver dysfunction is a topic of global concern with many advancing therapies being researched. Though vitamin D takes a center place, other therapies especially nutritional are also gaining ground. Vitamin D has gone beyond its role in skeletal disorders by showcasing its associations in other metabolic dysfunctions too. Result Epidemiological evidences show a correlation between the status of vitamin D and different forms of cancer. Vitamin D receptors and alterations in gene expression appear decisive in the development of chronic liver disorders. Nutritional status therefore plays a significant role in avoiding the complications related to liver dysfunctions, making it mandatory in maintaining vitamin D sufficiency in the body. Therapies with omega-3 fatty acids, antioxidants, amino acids, steroids also render benefits which could be further explored. Recent research on the progression of certain forms of liver cancer using vitamin D analogs like Seocalcitol EB 1089 has shown good promise. Conclusion The anti-inflammatory and immuno- regulatory properties of vitamin D makes its analogs, suitable candidates of better choice for the prevention and treatment of liver disorders and cancer