The Nonapeptide RWQWRWQWR: A Promising Molecule for Breast Cancer Therapy

Abstract

The palindromic nonapeptide H‐1RWQWRWQWR9‐NH2 (LfcinB (21–25)Pal) was synthetize and scaled following the good manufacturing practices (GMP) guidelines to obtained batches up to 1 g of pure peptide which evidencing their synthetic viability. Its cytotoxic effect was tested against breast cancer cell lines MDA‐MB‐231 and MCF‐7 and was dependent on concentration against both. The IC50 values were 135 μM and 66 μM, respectively. Against MCF‐7 the peptide exerts its greater cytotoxic effect at 135 μM, diminishing their cell viability to 21%. Furthermore, the palindromic peptide did not exhibit a significant cytotoxic effect against the nontumorigenic cells MCF‐12, BMEC (bovine mammary epithelial cells) or fibroblast, which confirms its selectivity. The cancerous cells treated at 135 μM for 2 h exhibited morphological changes like cellular shrinkage and rounded forms. Trough flow cytometry assays we evidence that 73% of the events were related to late apoptosis, and cells that exhibited mitochondrial membrane depolarization also had an increase in the relative expression of caspase‐3. Our results suggest that the LfcinB (21–25)Pal peptide has a cytotoxic effect against MCF‐7 mainly through apoptotic events which makes it a promising candidate for therapeutic agent.

Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

“…Also, the addition of Trp or another hydrophobic amino acid to this cationic sequence has improved the effect because of its ability to disrupt the cell membrane and reach intracellular targets . Both approaches have been tested in the palindromic peptide R-1-R, whose configuration of alternation of basic and hydrophobic residues induces an advantageous effect over the lactoferricin minimal motif, inducing cytotoxicity against breast MCF-7, MDA-MB-231, MDA-MB-468, and colorectal CaCo-2 cancerous cell lines while exhibiting no or significantly less activity on HEK-293, MCF-12, CEMB, and primary culture fibroblasts. ,, Also, a replacement of Arg to Lys residues has been made in this palindromic sequence; this approach does not improve its antibacterial activity or its cytotoxic effect.…”

“…22 Both approaches have been tested in the palindromic peptide R-1-R, whose configuration of alternation of basic and hydrophobic residues induces an advantageous effect over the lactoferricin minimal motif, inducing cytotoxicity against breast MCF-7, MDA-MB-231, MDA-MB-468, and colorectal CaCo-2 cancerous cell lines while exhibiting no or significantly less activity on HEK-293, MCF-12, CEMB, and primary culture fibroblasts. 6,15,23 Also, a replacement of Arg to Lys residues has been made in this palindromic sequence; this approach does not improve its antibacterial activity 24 or its cytotoxic effect. Modifications of the length of active peptides have been shown to result in a major improvement of their antimicrobial activity.…”

“…The same way against luminal breast cancer cell line MCF-7, an IC 50 of 66 μM was registered. Its selectivity has been tested in primary fibroblasts, noncancerous cells MCF-12, and bovine mammary cells BMEC, with minimum effect on them, , showing that the palindromic array enhanced the selective anticancer activity.…”

“…5 New alternatives such as antimicrobial peptides (AMPs) are being evaluated due to their fast interaction, reduced toxicity, good solubility, and ease of synthetic modification. 6 Some of these AMPs are cationic, which interact electrostatically with anionic components of the bacterial cell membrane, and since cancerous cells also have a negative cell membrane due to the impaired phospholipid in the external cell membrane and a higher expression of O-glycosylated mucins, a cytotoxic effect against cancerous cells is also evaluated. 7 Bovine lactoferricin (LfcinB) is a 25 amino acid AMP derived from bovine lactoferrin protein that has exhibited cytotoxic effects against different microorganisms like Gram-positive and Gramnegative bacteria and Candida spp.…”

Combining the Peptide RWQWRWQWR and an Ethanolic Extract of Bidens pilosa Enhances the Activity against Sensitive and Resistant Candida albicans and C. auris Strains

“…Several studies have demonstrated that the combination of drugs offers numerous advantages over monotherapy, which include reduced dosage, synergistic re- Similarly, Barragán-Cárdenas et al have reported that this palindromic peptide exhibits a rapid cytotoxic effect on breast cancer cells. They also tested its selectivity on primary fibroblasts, non-cancerous MCF-12 cells, and BMEC bovine mammary cells, with minimal effect on them [47,48].…”