Cytotoxicity of apo bovine ?-lactalbumin complexed with La3+ on cancer cells supported by its high resolution crystal structure.

ABSTRACT: Cancer remains one of the biggest threats to human society. There are massive demands for compounds to selectively kill cancerous cells. Earlier studies have shown that bovine ? -lactalbumin made lethal to tumor cells (BAMLET) becomes cytotoxic against cancer cells in complex with oleic acid {Hoque, M. et. al., PLoSOne 8, e68390 (2013)}. In our study, we obtained bovine ?-lactalbumin complexed with lanthanum ion (La3+-B-?-LA) and determined its high resolution crystal structure. The natural calcium binding site of bovine ?-lactalbumin is replaced by lanthanum. The La3+ complex formation by B-?-apo-LA was also supported by various biophysical methods. Interestingly, our complex, La3+-B-?-LA exhibits much greater anticancer activity against breast cancer cells as compared to the reported BAMLET-oleic acid complex. This study shows that La3+-B-?-LA complex is preferentially more toxic to MCF-7 cells as compared to KB (oral cancer) and HeLa (cervical) cells, while almost non-toxic to the healthy cells that we studied. Our data indicates that the cytotoxicity of La3+-B-?-LA against cancer cells is through apoptotic path way. The higher anticancer activity of La3+-B-?-LA is attributable to the requisite structural changes induced in the protein by La3+ binding as supported by the crystal structure of the complex.

SUBMITTER: Yarramala DS 

PROVIDER: S-EPMC6370903 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature