Structure and stability analysis of cytotoxic complex of camel α-lactalbumin and unsaturated fatty acids produced at high temperature

J Biomol Struct Dyn. 2011 Jun;28(6):919-28. doi: 10.1080/07391102.2011.10508618.

Abstract

α-Lactalbumin α-La), together with oleic acid can be converted to a complex, which kills tumor cells selectively. Cytotoxic α-La -oleic acid and α-La -linoleic acid complexes were generated by adding fatty acid to camel holo α-La at 60 ° C (referred to as La-OA-60 and La-LA-60 state, respectively). Structural properties of these complexes were studied and compared to the camel α-La. The experimental results show that linoleic acid induces α-La partial unfolding but oleic acid does not change the protein structure significantly. Also the stability of La-OA-60 and La-LA-60 toward thermal denaturation was measured. The order of temperature at the transition midpoint is as follows: La-LA-60 < La-OA-60 < α-La. La-OA-60 complex inhibited tubulin polymerization in vitro. Although the structures of La-OA-60 and La-LA-60 were different, these two complexes had similar cytotoxic effect to DU145 human prostate cancer cells. Samples of La-OA-60 that have been renatured after denaturation lost the specific biological activity toward tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Calcium / chemistry
  • Calcium / metabolism
  • Cell Line, Tumor
  • Circular Dichroism
  • Computer-Aided Design
  • Drug Design
  • Drug Discovery
  • Hot Temperature
  • Humans
  • Lactalbumin / chemistry*
  • Lactalbumin / metabolism
  • Lactalbumin / pharmacology*
  • Linoleic Acid / chemistry*
  • Linoleic Acid / metabolism
  • Linoleic Acid / pharmacology
  • Male
  • Oleic Acid / chemistry*
  • Oleic Acid / metabolism
  • Oleic Acid / pharmacology
  • Prostatic Neoplasms / drug therapy
  • Protein Conformation
  • Protein Folding
  • Protein Stability
  • Protein Structure, Secondary
  • Spectrometry, Fluorescence
  • Tubulin / biosynthesis

Substances

  • Antineoplastic Agents
  • Tubulin
  • Oleic Acid
  • Lactalbumin
  • Linoleic Acid
  • Calcium