Modulation of the activity of certain genes involved in tumor cell metabolism in the presence of the cytotoxic peptides defensin and cathelicidin LL37

Abstract

It is common knowledge that some natural antimicrobial peptides also have a tumoricidal effect. We have shown that the peptides defensin and cathelicidin LL37 have cytostatic effects on human tumor cell lines HT29 (colorectal carcinoma) and A549 (alveolar carcinoma). In order to determine the modulating mechanism of these peptides we assessed the gene expression of the AKT, HIF-1α, XBP, NRF2, PERK, CHOP, BCL2, IRE1α and PI3K molecular targets involved in the survival, growth, proliferation and apoptosis pathways of tumor cells in the presence or absence of the studied peptides. Thus, this research enabled us to determine molecular markers and methods of assessment and monitoring of tumor cell cytotoxicity by high-performance molecular biology techniques. Defensin and cathelicidin LL37 activated tumor cell apoptosis, especially for the HT29, but also for A549 line, by increasing gene expression of CHOP and by lowering BCL2 gene expression. Oxidative stress determined the increase in gene expression of XBP, which directly influenced CHOP. The decrease in NRF2 gene expression highlighted the inhibition of cell proliferation, while the decrease in HIF1α gene expression evidenced the decrease in cell survival.

[Editorial] Highlights of the 3rd conference of the Romanian Association of Immuno‑Dermatology and the 37th conference of the Romanian Society of Immunology held in Bucharest between September 19 and 22, 2019

“…Ștefanache et al (11) have demonstrated in previous studies that that the peptides, defensin and cathelicidin LL37, exert cytostatic effects on the following human tumor cell lines: HT29 (colorectal adenocarcinoma) and A549 (alveolar carcinoma). In their original article, entitled ‘Modulation of the activity of certain genes involved in tumor cell metabolism in the presence of the cytotoxic peptides defensin and cathelicidin LL37’, they assessed the gene expression of the AKT, HIF-1α, XBP, NRF2, PERK, CHOP, BCL2, IRE1α and PI3K molecular targets involved in the survival, growth, proliferation and apoptosis pathways of tumor cells in the presence or absence of the peptides examined.…”