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Exp Ther Med. 2019 Dec;18(6):5033-5040. doi: 10.3892/etm.2019.8117. Epub 2019 Oct 21.

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

Author information

1
Department of Pathophysiology, University of Medicine and Pharmacy 'Grigore T. Popa', 700115 Iaşi, Romania.
2
Department of Implantology, Dental Medicine, 700115 Iaşi, Romania.
3
Regional Institute of Oncology Iasi, 700115 Iaşi, Romania.
4
Department of Internal Medicine, University of Medicine and Pharmacy 'Grigore T. Popa', 700115 Iaşi, Romania.
5
Rehabilitation Hospital of Iasi, Rheumatology Clinic, University of Medicine and Pharmacy 'Grigore T. Popa', 700115 Iaşi, Romania.

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.

KEYWORDS:

cathelicidin; defensin; gene expression

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