It is well known that blood lipoproteins (LPs) are multimolecular complexes of lipids and proteins that play a crucial role in lipid transport. High-density lipoproteins (HDL) are a class of blood plasma LPs that mediate reverse cholesterol transport (RCT)—cholesterol transport from the peripheral tissues to the liver. Due to this ability to promote cholesterol uptake from cell membranes, HDL possess antiatherogenic properties. This function was first observed at the end of the 1970s to the beginning of the 1980s, resulting in high interest in this class of LPs. It was shown that HDL are the prevalent class of LPs in several types of living organisms (from fishes to monkeys) with high resistance to atherosclerosis and cardiovascular disorders. Lately, understanding of the mechanisms of the antiatherogenic properties of HDL has significantly expanded. Besides the contribution to RCT, HDL have been shown to modulate inflammatory processes, blood clotting, and vasomotor responses. These particles also possess antioxidant properties and contribute to immune reactions and intercellular signaling. Herein, we review data on the structure and mechanisms of the pleiotropic biological functions of HDL from the point of view of their evolutionary role and complex dynamic nature.

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Background: The goal of this study was to evaluate anticancer and testosterone-inhibitory effect of 2‘-[(E) androst-5-en-17- ylidene]methyl-4‘,5‘-dihydro-1‘,3‘-oxazole-3β-oleate (Alsevirone-NF). Materials and Methods: PC-3, DU-145, LnCap and 22rv1 prostate cancer cell lines were used for MTT assay. 22rv1 subcutaneous cancer xenografts in Balb/c nude mice were used for in vivo efficacy experiment. Testosterone level was determined after repeated administration of Abiraterone 20, 100 or 200 mg/kg vs Alsevirone-NF 5, 25 or 50 mg/kg daily for 14 days. Results: Alsevirone-NF induced more significant cytotoxicity against PC3, 22rv1 and DU-145 cell lines compared to Abiraterone or Alsevironetreated control: IC50 7.1 vs 20.6 vs 29.1 µg/ml, 7.7 vs 20.0 vs 12.7 µg/ml, 3.8 vs 43.4 vs 8.5 µg/ml, respectively. IC50 in LnCap cells was almost equal for all three studied agents, 29.2 vs 26.2 vs 30.2 µg/ml for Abiraterone, Alsevirone and Alsevirone-NF. In gonadectomized mice, significant reduction of testosterone level was observed in mice received Alsevirone-NF in a maximum single dose of 50 mg/kg (cumulative dose 700 mg/kg): 0.2 nmol/l vs 0.57 nmol/l in control group and 0.83 nmol/l in Abiraterone group, single dose 100 mg/kg. Statistically significant anticancer effect in vivo was obtained on day 11 after start of treatment: Abiraterone T/C = 27% (p<0.05), Alsevirone-NF single dose 1200 mg/kg Т/С = 45% (p<0.05). Conclusion: Alsevirone-NF exhibited higher cytotoxic activity, comparable anticancer effect in 22rv1-bearing Balb/c nude mice and provided more significant reduction of testosterone level in gonadectomized mice in direct comparison against Abiraterone.