Salmon Protein Hydrolysate Potentiates the Growth Inhibitory Effect of Bicalutamide on Human Prostate Cancer Cell Lines LNCaP and PC3 by Modulating Iron Homeostasis

Abstract

Prostate cancer is a common cause of cancer death in men. In advanced stages of prostate cancer, androgen deprivation therapy (ADT) is initiated. Despite ADT, prostate cancers invariably progress to become androgen independent. A growing body of evidence implicates iron dysmetabolism in prostate cancer progression. A bioactive peptide-rich salmon protein hydrolysate (SPH) has previously been demonstrated to modulate iron homeostatic mechanisms. In the present study, the anticancer effect of SPH and bicalutamide co-treatment on LNCaP and PC3 prostate cancer cell proliferation was investigated. Our results found that SPH potentiates the anti-proliferative effect of bicalutamide in a dose-dependent manner for both cell lines. In the presence of 160 µg/mL SPH, co-treatment with 1.0 µM bicalutamide decreased LNCaP cells’ relative colony survival from 25% (1.0 µM bicalutamide monotreatment) to 2% after culturing for 12 days. For PC3 cells, the relative colony survival diminished from 52% (10.0 µM bicalutamide) to 32% at an SPH concentration of 160 µg/mL. Gene expression profiling, employing quantitative real-time PCR, revealed that the inhibitory effects were related to significant FTH1 up-regulation with a concomitant TFRC down-regulation. In conclusion, our results provide in vitro evidence that SPH potentiates the growth inhibitory effect of bicalutamide on prostate cancer cells by modulating iron homeostasis mechanisms.

Assessing the Potential of Small Peptides for Altering Expression Levels of the Iron-Regulatory Genes FTH1 and TFRC and Enhancing Androgen Receptor Inhibitor Activity in In Vitro Prostate Cancer Models

“…Lastly, after incubation with FT-005-E, the colony survival rate of VCaP cell colonies decreased to 23%. We may summarize this by stating that a general agreement appears to exist between the data and results presented herein and those reported in our previous in vitro study employing an SPH and bicalutamide treatment protocol in PCa cells [47].…”

“…Previous preliminary studies by the authors revealed that a soluble protein hydrolysate (SPH) was capable of significantly altering the expression of ferritin heavy chain 1 (FTH1) and transferrin receptor (TFRC) expression in gingival epithelial cells [46]. In a followup study, this SPH was shown to significantly enhance the efficacy of a first-generation antiandrogen in two types of PCa cells [47]. The extent to which gene modulation was altered corresponded to the magnitude of the effect on suppressing growth of PCa cells in the same study.…”

Marine Natural Products with Activities against Prostate Cancer: Recent Discoveries

“…In particular, Bjerknes et al showed that co-treatment of 160 µg/mL SPH with 1.0 µM bicalutamide decreased the relative colony survival of LNCaP cells from 25% to 2% after culturing for 12 days. The inhibitory effects were related to significant ferritin heavy chain 1 (FTH1) up-regulation [ 111 ].…”

Marine Compounds and Cancer: Updates 2022

“…Bjerknes and colleagues characterized a salmon protein hydrolysate and showed its synergistic effect in combination with bicalutamide in human prostate cancer cells. The mechanism of this phenomenon was described as the modulation of iron homeostasis [22]. The group of von Amsberg investigated the cytotoxic anticancer activity of N-methylpretrichodermamide B in drug-resistant prostate cancer cells in vitro.…”