Research Projects

Oral cancer belongs to a group of cancers that are collectively called as head and neck carcinoma. It develops in the squamous cells present in the tongue, mouth, gingiva and lips. Oral cancer is one the serious health challenges of developing nations and it is the 6th most prevalent tumor in the world. The new cancer cases are estimated to rise to 19.3 million per year by 2025. Oral squamous cell carcinoma (OSCC) is a malignant epithelial neoplasm that affects the head and neck region and contributes to around 84-97% of the oral cancer. Previously, studies have reported that overexpression of AURKA contributes to the progression of OSCC. AURKA plays a very critical role in the development of various cancers and is associated with poor prognosis. It was reported that in lung cancer AURKA overexpression is responsible for the evolution of resistance to EGFR inhibitors. To inhibit the oncogenic functions of AURKA, researchers are making enormous efforts to develop inhibitors of AURKA. Small molecule inhibitors of AURKA that bind to the ATP-binding catalytic pocket, namely, are currently under clinical investigation. Whereas AURKA inhibitors that bind to an allosteric site such as, are only available as experimental inhibitors. The most commonly used AURK inhibitor alisertib (MLN8237) has very narrow selectivity and exhibits anti-tumor activities only when combined with various chemotherapeutic drugs. Although a couple of AURKA inhibitors have entered the clinic investigation they cause side effects such as febrile neutropenia, hypertension, fatigue, stomatitis and gastrointestinal toxicity. Therefore, lack of AURKA inhibitors with high specificity and low toxicity is the key driver of research initiatives towards designing more novel drugs that can potentially circumvent the tumor burden. In the present work 45 plant derived anticancer peptides were modeled. Using molecular docking analysis it was found that peptide. Using molecular docking analysis, it was observed that three peptides namely, AP01279, AP01280 and AP01281 derived from Viscum album binds to the catalytic pocket of AURK with higher binding affinity of -234.28, -230.21 and -231.71Kcal/mol respectively. Also, using site directed mutagenesis, it was found that mutations namely, Y13W, E24K and A37E on AP01279 enhances the binding affinity with AURKA. Likewise, F18L mutation on AP01280 and AP01281 increases the binding affinity with AURKA. On contrary, Y13L, F18D and F18D mutations on AP01279, AP01280 and AP01281 reduces binding affinity with AURKA respectively. Therefore, Y13W, E24K A37E AP01279 mutant peptide will be generated to inhibit the ATPase activity of AURKA. Since overexpression of AURKA is associated with progression of oral cancer, the effect of engineered AP01279 peptide on oral cancer cell lines will be evaluated.