Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer.

The aim of the manuscript is to discuss the influence of plant polyphenols in overcoming multidrug resistance in four types of solid cancers (breast, colorectal, lung and prostate cancer). Effective treatment requires the use of multiple toxic chemotherapeutic drugs with different properties and targets. However, a major cause of cancer treatment failure and metastasis is the development of multidrug resistance. Potential mechanisms of multidrug resistance include increase of drug efflux, drug inactivation, detoxification mechanisms, modification of drug target, inhibition of cell death, involvement of cancer stem cells, dysregulation of miRNAs activity, epigenetic variations, imbalance of DNA damage/repair processes, tumor heterogeneity, tumor microenvironment, epithelial to mesenchymal transition and modulation of reactive oxygen species. Taking into consideration that synthetic multidrug resistance agents have failed to demonstrate significant survival benefits in patients with different types of cancer, recent research have focused on beneficial effects of natural compounds. Several phenolic compounds (flavones, phenolcarboxylic acids, ellagitannins, stilbens, lignans, curcumin, etc.) act as chemopreventive agents due to their antioxidant capacity, inhibition of proliferation, survival, angiogenesis, and metastasis, modulation of immune and inflammatory responses or inactivation of pro-carcinogens. Moreover, preclinical and clinical studies revealed that these compounds prevent multidrug resistance in cancer by modulating different pathways. Additional research is needed regarding the role of phenolic compounds in the prevention of multidrug resistance in different types of cancer.

Epigallocatechin 3-O-gallate induces 67 kDa laminin receptor-mediated cell death accompanied by downregulation of ErbB proteins and altered lipid raft clustering in mammary and epidermoid carcinoma cells.

Since the administration of synthetic medicines is associated with drug resistance and undesired side effects, utilization of natural compounds could be an alternative and complementary modality to inhibit or prevent the development of tumors. Epigallocatechin 3-O-gallate (EGCG, 1), the major flavan component of green tea, and genistein (2), a soy isoflavonoid, are known to have chemopreventive and chemotherapeutic effects against cancer. This study demonstrated that both flavonoids inhibit cell proliferation, an effect enhanced under serum-free conditions. Compound 1, but not 2, induced downregulation of ErbB1 and ErbB2 in mammary and epidermoid carcinoma cells, and its inhibitory effect on cell viability was mediated by the 67 kDa laminin receptor (67LR). While 1 was superior in inducing cell death, 2 was more efficient in arresting the tumor cells in the G2/M phase. Furthermore, number and brightness analysis revealed that 1 decreased the homoclustering of a lipid raft marker, glycosylphosphatidylinositol-anchored GFP, and it also reduced the co-localization between lipid rafts and 67LR. The main conclusion made is that the primary target of 1 may be the lipid raft component of the plasma membrane followed by secondary changes in the expression of ErbB proteins. Compound 2, on the other hand, must have other unidentified targets.

[Selenium deficiency and infertility. Andrologic aspects]. / Szelénhiány és meddôség. Andrológiai vonatkozások.

Absolute selenium deficiency in human is very rare, although suboptimal daily selenium intake may lead to an unrecognized relative deficiency. Among the many consequences ascribed to decreased selenium level, the effect on male fertility is summarised by the authors. Implications from biochemical, animal experimental and human research are discussed.

Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study.

A randomized, placebo-controlled clinical pilot study was performed in order to examine the effect of magnesium-orotate in male idiopathic infertility. Ten males were treated daily for 90 consecutive days with 3000 mg magnesium-orotate (Magnerot) tablets (Group M). As a control, ten other males were treated in the same way with placebo (Group P). Conventional microscopic sperm characteristics (sperm concentration, motility ratio, total number of motile sperm cells, normal morphology ratio), plus total and ionized magnesium levels in seminal plasma and blood serum were evaluated both prior to treatment and on day 90, at the conclusion of the study. No significant changes in sperm characteristics, blood ionized or total Mg, or ejaculate total Mg levels were detected. However, ejaculate ionized Mg levels increased in Group M from 0.18 +/- 0.05 to 0.30 +/- 0.05 (mmol/l; mean +/- SD, p < 0.05). Within the observation period of 3 months, one pregnancy occurred in the partner of a male from Group M. In conclusion, magnesium-orotate treatment at a dose of 3000 mg/day leads neither to a significant improvement of sperm variables nor does it increase the pregnancy rates of female partners of treated males as compared to those of controls. Thus, magnesium-orotate treatment was not shown to be effective therapy for idiopathic male infertility.