title: Structure and stability analysis of cytotoxic complex of camel α-lactalbumin and unsaturated fatty acids produced at high temperature.
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.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Maliheh S
authors.initials: MS
authors.lastname: Atri
authors.forename: Ali A
authors.initials: AA
authors.lastname: Saboury
authors.forename: Ali A
authors.initials: AA
authors.lastname: Moosavi-Movahedi
authors.forename: Bahram
authors.initials: B
authors.lastname: Goliaei
authors.forename: Yahya
authors.initials: Y
authors.lastname: Sefidbakht
authors.forename: Hamid Hadi
authors.initials: HH
authors.lastname: Alijanvand
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sharifzadeh
authors.forename: Amir
authors.initials: A
authors.lastname: Niasari-Naslaji
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D017076:Computer-Aided Design; D015195:Drug Design; D055808:Drug Discovery; D006358:Hot Temperature; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D019787:Linoleic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D019301:Oleic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D014404:Tubulin / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D019301:Oleic Acid; D007768:Lactalbumin; D019787:Linoleic Acid; D002118:Calcium