Cyclophosphamide Induced Modificationsof Human Antiproteinase Alpha-2-Macroglobulin
Cancer is a group of diseases which involves abnormal cell growth with the potential to invade or spread to other parts of the body.In cancer, cells divide and grow uncontrollably, forming malignant tumors, which mayinvade nearby parts of the body.Cyclophosphamide is an anti-cancer chemotherapy drug which belongs to a class of drugs called alkylating agents.Cyclophosphamide is administered intravenously and is used for treating recurrent testicular cancer and germ cell tumors, Non-Hodgkin’s lymphoma and bladder cancer.
Alpha-2-Macroglobulin(α2M) is a major non-immunoglobulin protein found in human plasma where it acts as major broad spectrum antiproteinase and is able to inhibit variety of proteinases. It may also act as a carrier protein; it binds to numerous growth factors and cytokines. α2M was until recently believed to be “fail safe” antiproteinase at inflammatory site as very few physiological or environmental agents are known to disrupt its function. The study intends to explore the effect of cyclophosphamide on the structure and function of α2M using spectral and fluorescence analysis and monitoring antiproteinase α2M activity by amidase assay. Change in secondary structure of α2M was confirmed by circular dichroism.Our preliminary results suggest thatcyclophosphamide alters the antiproteolytic activity of α2M. The gross α2M structure remains largely unaffected though it did undergo subtle changes as suggested by absorbtion spectra and fluorescence analysis. Disruption of antiproteinase activity of α2M have far reaching consequences as it creates crack in antiproteinase shield of the body resulting in heightened proteolytic activity, though this observation is still to be explored in detail .