Breast cancer is one of the main causes of premature
death in women;
current treatments have low selectivity, generating strong physical
and psychological sequelae. The palindromic peptide R-1-R (RWQWRWQWR)
has cytotoxic activity against different cell lines derived from cancer
and selectivity against noncancerous cells. To determine if changes
in the charge/length of this peptide increase its activity, six peptides
were obtained by SPPS, three of them with addition of Arg at the N,
C-terminal or both and three with deletion of Arg at the N, C-terminal
or both. The cytotoxic and selective activities were evaluated against
MCF-7, MDA-MB-231, and MCF-12 cell lines and fibroblast primary cell
culture, evidencing that the RR-1-R peptide with the inclusion of
Arg in the N-terminal end maintained selectivity and increased cytotoxicity
against lines derived from breast cancer. The effect of this addition
regarding the type of induced cell death was evaluated by flow cytometry,
showing very low rates of necrosis and a significant majority of apoptotic
events with activation of both Caspase 8 and Caspase 9. This work
allowed us to find a modification that generates a peptide with greater
cytotoxic effects and can be considered a promising molecule for other
approaches to improve anticancer peptides.