Abhay Kumar Singh, Rahul Kumar, Rajinder Parsad, Sharmistha Dey
Department of Biophysics, and Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India – 110 029, India.
Cancer is a major health problem worldwide and is fast becoming one of the most important causes of morbidity and mortality in children and adults. Most of the cancer patients are diagnosed at late stage in which the cancer is too far advancer to be cure. Unfortunately, there has been little improvement in the early detection of cancer. So, many researchers are working hard to find the hallmarks of cancer which will indicate how, where and when the cancer is going to develop. They make use of various approaches in searching for proteins, rare variants, new gene pathways that lead to oncogenesis in order to find biomarkers that will be of use to clinicians and possibly to biotech and pharmaceutical companies looking to create new therapies. This work involves to quantitate the serum COX-2 in breast and oral cancer, its effect after chemotherapy to establish serum COX-2 as a prognostic marker and the inhibition of COX-2 by structure based designed peptide inhibitors. The evaluation of COX-2 was done by real time Surface Plasmon Resonance (SPR) technology in BIAcore 2000 and ELISA. The serum COX-2 was found to be significantly (P>0.0001) elevate in the cancer patients compare to the normal control. Thus, COX-2 can be a potent biological molecular marker for prognosis of cancer and can be a good therapeutic target for drug designing. Hence, study was followed by the design of specific peptide inhibitors based on the structure of active site of COX-2. Ten tri peptides were screened biochemically as an inhibitor of COX-2 and tested for anti cancer activity in KB and MCF-7 cell line for oral and breast cancer respectively. Among these ten peptides one peptide (P1) had shown more than 80% inhibition against COX-2 and significantly reduced viability and inhibited growth/proliferation induced cytotoxicity and apoptosis in tumor cells. The preliminary in vivo study had also shown that anticancer peptide P1 as better therapeutic effects in early cases of experimentally-induced bovine papillomavirus (BPV) tumours in hamsters. More studies are required to support this observation. Read more…