Silver nanoparticles exhibit size-dependent differential toxicity and induce expression of syncytin-1 in FA-AML1 and MOLT-4 leukaemia cell lines

Abstract

Human endogenous retrovirus (HERV) sequences make up approximately 8% of the human genome and increased expression of some HERV proteins has been observed in various pathologies including leukaemia and multiple sclerosis (MS). However, little is known about the function of these HERV proteins or environmental factors which regulate their expression. Silver nanoparticles (AgNPs) are used very extensively as antimicrobials and antivirals in numerous consumer products although their effect on the expression of HERV gene products is unknown. Cell proliferation and cell toxicity assays were carried out on human acute T lymphoblastic leukaemia (MOLT-4) and Fanconi anaemia associated acute myeloid leukaemia (FA-AML1) cells treated with two different sizes of AgNPs (7 nm and 50 nm diameter). RT-PCR and Western blotting were then used to the assess expression of HERV-W syncytin-1 mRNA and protein in these cells. FA-AML1 cells were more sensitive overall than MOLT-4 to treatment with the smaller 7 nm sized AgNp's being the most toxic in these cells. MOLT-4 cell were more resistant and showed no evidence of differential toxicity to the different sized particles. Syncytin-1 mRNA and protein were induced by both 7 and 50 nm AgNPs in both cell types yet with different kinetics. In summary, the observation that AgNPs induce expression of syncytin-1 in FA-AML1 and MOLT-4 cells at doses as little as 5 µg/ml is grounds for concern since this protein is up-regulated in both malignant and neurodegenerative diseases. Considering the widespread use of AgNPs in the environment it is clear that their ability to induce syncytin-1 should be investigated further in other cell types.3

Human endogenous retroviruses in cancer: Expression, regulation and function (Review)

“…The mechanisms of HERV activation by viruses are relatively clear whereas those by physical and chemical factors remain uncertain (54,82,83). Hydroquinone (55), cupric ion (84), silver nanoparticles (85), and ultraviolet exposure (86), as well as hypoxia phenomenon (70) can influence the expression of HERVs in tumor cell lines. However, the underlying mechanism remains unknown ( Fig.…”

A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches

“…The published literature describes both upstream regulation of HERV expression as well as downstream effects of increased HERV activity [43,86]. Alqahtani et al found that cellular stress from contact with silver nanoparticles increases HERV-W Env protein expression through a possible survival response to an increase in reactive oxygen species (ROS) [86].…”

Human endogenous retrovirus regulates the initiation and progression of cancers (Review)

“…Blood cancers. The expression of HERVs has been reported in acute myeloid leukemia (AML) (12,(92)(93)(94), acute lymphoblastic leukemia (ALL) (12,93,94), acute mixed lineage leukemia (AMLL) (94), chronic myeloid leukemia (CML) (12), chronic lymphoblastic leukemia (CLL) (94), chronic mixed myeloid leukemia (CMML) (92), non-Hodgkin's lymphoma (NHL) and other lymphomas (94)(95)(96), essential thrombopenia (ET) (97), and myelodysplastic syndrome (MDS) (53) (Table II). The Np9 protein expressed by HERV-K activates a cascade of cellular signaling pathways (β-catenin, ERK, AKT, and Notch1), which helps in the proliferation of leukemia cells by increasing le1ukemia stem and progenitor cells (2,20).…”