Abstract
Background: 6′-Sialyllactose (6SL) displays a wide range of the bioactive benefits, such as anti-proliferative and anti-angiogenic activities. However, the therapeutic effects of 6SL on benign prostatic hyperplasia (BPH) remain unknown. Methods: Six-week-old male Wistar rats (n = 40) were used for in vivo experiments. All rats were castrated and experimental BPH was induced in castrated rats by intramuscular injection of testosterone, with the exception of those in the control group. Rats with BPH were administrated finasteride and 0.5 or 1.0 mg/kg 6SL. Furthermore, the inhibitory effects of 6SL on human epithelial BPH cell line (BPH-1) cells were determined in vitro. Results: Rats with BPH exhibited outstanding BPH manifestations, including prostate enlargement, histological alterations, and increased prostate-specific antigen (PSA) levels. Compared to those in the BPH group, rats in the 6SL group showed fewer pathological changes and normal androgen events, followed by restoration of retinoblastoma protein (pRb) and cell cycle-related proteins. In BPH-1 cells, treatment with 6SL significantly suppressed the effects on the androgen receptor (AR), PSA, and E2F transcription factor 1 (E2F1)-dependent cell cycle protein expression. Conclusions: 6SL demonstrated anti-proliferative effects in a testosterone-induced BPH rat model and on BPH-1 cells by regulating the pRB/E2F1–AR pathway. According to our results, we suggest that 6SL may be considered a potential agent for the treatment of BPH.
Highlights
Human milk oligosaccharides (HMOs) are major components of human breast milk, consisting of a complex mixture
Had notably enlarged prostates and showed hyperemia to rats the ventral prostate (VP) and dorsolateral prostate (DLP) were dissected and the macroscopic features compared of benign prostatic hyperplasia (BPH) were in theevaluated
Our results revealed overexpression of pRb/E2F transcription factor 1 (E2F1), cyclin A, Cdk2, and cyclin D1 proteins in BPH-1 cells, whereas 60 -Sialyllactose (6SL) treatment downregulated the expression of cell cycle regulatory proteins, consistent with inhibition of pRb/E2F1 expression
Summary
Human milk oligosaccharides (HMOs) are major components of human breast milk, consisting of a complex mixture. More than 130 different HMOs have been identified [1]. Among these, sialylated HMOs are thought to be important components of HMOs that increase the nutritional value of human milk and show beneficial effects [2,3]. Large amounts of sialylated HMOs are present in colostrum (1–3.3 g/L) and 60 -Sialyllactose (6SL) is the most abundant fraction in sialylated. A broad range of functions have been attributed to HMOs and recent studies have detailed the inhibitory effects of HMOs and sialylated HMOs on tumorigenesis [5,6].
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