The cytotoxicity BAMLET complex is regulated by the dispersion of the oleic acid and independent of α-lactalbumin component

Y. Delgado, M. Morales-Cruz, J. Hernández-Román, G. Hernández1 and K. Griebenow
University of Puerto Rico, US

Keywords: BAMLET, fatty acids, α-lactalbumin, cytotoxicity, cancer therapy, oleic acid, linoleic acid

Summary:

Designing effective cancer treatments is a top priority for health related research. Traditional chemo-therapies often still utilize combinations of cytotoxic drugs that kill metabolically active cells.A HAMLET/BAMLET complex composed of oleic acid (OA) coupled to human or bovine α-lactalbumin (α-LA) has been shown to have powerful toxic properties 1-3 but its main cytotoxic constituent to kill cancer cells is still under debate.Our results show that all the BAMLET complexes have an approximate size of 200 nm. BAMLET complexes were incubated at a proteolityc environment to elucidate that the binding sites of OA are at the α-LA surface to form the micelle. In vitro experiments demonstrated that native or partially unfolded bovine α-LA lacks to activate tumoricidal action by itself. Nevertheless, we elucidated that OA alone kills cancer cells at equimolar concentrations to BAMLET. OA modified with PDPH linker had no a significant effect on its cytotoxicity. Compared to OA, LinOA showed strong effect to induce cytotoxicity, and even coupled to α-LA. However, cellular response was absent for SA. Our data highlight that the cytotoxicity of the BAMLET complex is exclusively due to the unsaturation of OA and α-LA just represent the carrier for the delivery.