Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium

Abstract

Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans. Moreover, our previous studies showed that the immunosuppressive effects of ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cells. We also verified that this immunosuppression facilitated development of cancer. Here, we performed gene expression microarray analysis in splenic NK cells from mice treated for 14 days with ptaquiloside (5.3 mg/kg) and/or selenium (1.3 mg/kg) to identify gene transcripts altered by ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium. Transcriptome analysis of ptaquiloside samples revealed that 872 transcripts were expressed differentially (fold change>2 and p<0.05), including 77 up-regulated and 795 down-regulated transcripts. Gene ontology analysis mapped these up-regulated transcripts to three main biological processes (cellular ion homeostasis, negative regulation of apoptosis and regulation of transcription). Considering the immunosuppressive effect of ptaquiloside, we hypothesized that two genes involved in cellular ion homeostasis, metallothionein 1 (Mt1) and metallothionein 2 (Mt2), could be implicated because Mt1 and Mt2 are responsible for zinc homeostasis, and a reduction of free intracellular zinc impairs NK functions. We confirm these hypotheses and show increased expression of metallothionein in splenic NK cells and reduction in free intracellular zinc following treatment with ptaquiloside that were completely prevented by selenium co-treatment. These findings could help avoid the higher susceptibility to cancer that is induced by P. aquilinum-mediated immunosuppressive effects.

Bovine Papillomavirus Type 2 Infection and a Series of Mesenchymal Tumors of the Urinary Bladder in Cattle

“…It is well known that PT can cause toxicity to the immune system, which could contribute to the activation of a latent and/or subclinical urothelial BPV-2 infection resulting in neoplasia [13]. PT is a powerful immune suppressor that is genotoxic for lymphocytes [11, 15–17] and depresses NK cell activities [18]. …”

Multiple Effects of Bracken Fern under in vivo and in vitro Conditions

“…It was also verified that selenium supplementation prevents decrease in NK cytotoxicity which is caused by p. aquilinum (Latorre et al, 2011). In 2013 researchers showed that selenium prevents carcinogenic effects caused by immunosuppressive effects of bracken fern (Latorre et al, 2013). Furthermore, ptaquiloside involved in bracken may also promote carcinogenicity by decreasing immune supervision against lately arising tumors (Gil da Costa et al, 2012).…”

Ferns and Lycopods—A Potential Treasury of Anticancer Agents but Also a Carcinogenic Hazard

“…In fact, one single dose of bracken extracts induced both structural and numerical chromosome aberrations in Swiss mice (Almeida Santos et al ., ). Bracken also exhibits a significant immunosuppressive effect, reducing natural killer cells, which could undermine tumour surveillance (Latorre et al ., ).…”