Anticancer peptide SVS-1: efficacy precedes membrane neutralization

Abstract

Anticancer peptides are polycationic amphiphiles capable of preferentially killing a wide spectrum of cancer cells relative to noncancerous cells. Their primary mode of action is an interaction with the cell membrane and subsequent activation of lytic effects; however, the exact mechanism responsible for this mode of action remains controversial. Using zeta potential analyses we demonstrate the interaction of a small anticancer peptide with membrane model systems and cancer cells. Electrostatic interactions have a pivotal role in the cell killing process, and in contrast to the antimicrobial peptides action cell death occurs without achieving full neutralization of the membrane charge.

Figure 1

Zeta potential measurements of 200 μM POPC and POPC:POPS 40:60 mixture after 30 minutes incubation and stabilization with SVS-1 and SVS-2 at 37°C. Triangles POPC, circles POPC:POPS 40:60, black symbols SVS-1 and grey symbols SVS-2. Error bars represent the standard deviation of at least two independent experiments.

Figure 2

Zeta potential of A549 (lung carcinoma) cells in the presence of SVS-1 and SVS-2. At 2.6×10⁵ cells/ml cells were incubated and stabilized for 30 minutes with different peptide concentrations and the potential was measured at 37°C. Error bars represent the standard deviation of at least two independent measurements.

Figure 3

In vitro cytotoxicity of SVS-1 and SVS-2 peptide toward A549 lung carcinoma evaluated at 24h after addition of the peptides. Data for SVS-1 was taken from reference . Error bars represent standard deviation of at least three independent experiments.