Oxaliplatin Induced Modificationsof Human Antiproteinase Alpha-2-Macroglobulin
Canceris a group of diseases which involves abnormal cell growth with the potential to invade or spread to other parts of the body. Oxaliplatin is an anticancer chemotherapy drug used to treat colon or rectal cancer. It is often given in combination with other anticancer drugs (fluorouracil and leucovorin).Oxaliplatin in plasma rapidly undergoes non-enzymatic transformation into reactive compounds because of displacement of the oxalate group, platinum complexes enter the cell, where they have cytotoxic properties.Alpha-2-macroglobulin (α2M) is a class of antiproteinases which can trap almost all classes of proteinases without direct blockage of their active site. α2M has many diversified and complex functions of binding, targeting and transportation due to the presence of multiple reactive sites. The most important function of α2M is the inhibition of proteinases. Our studies explored the interaction of oxaliplatin with α2M and analysed oxaliplatin induced structural alteration to the α2M. The result suggests that oxaliplatin decreases the antiproteolytic potential and causes structural and functional change in human α2M. UV-visible absorption spectroscopy confirms the formation of α2M- oxaliplatin complex. Fluorescence analysis shows significant quenching in fluorescence intensity of α2M upon binding with oxaliplatin. Secondary structure of α2M also undergoes a slight change upon complexation with the drug as evident by shift in negative ellipticity in far UV CD spectroscopy. Our results suggests drug oxaliplatin does interact with plasma inhibitor α2M and the protein consequently undergoes structural and functional modifications
Keywords - Oxaliplatin, Anticancer Drug, Alpha-2-Macroglobulin, Antiproteinase.