Title

Anti-Cancer Activity of Synthetic Analogues of Curcumin and Pancreastatin Alone and in Combination with Piperlongumine in Models of Astrocytoma

Streaming Media

Type of Proposal

Oral presentation

Start Date

24-3-2015 2:00 PM

End Date

24-3-2015 2:50 PM

Faculty

Faculty of Science

Faculty Sponsor

Siyaram Pandey

Importance of the Project

In 2012, 14.1 million adults in the world were diagnosed with cancer in 2012. In that year, there were 8.2 million deaths from cancer in the world (Cancer Research UK). Astrocytoma is a malignant type of glioma (brain cancer) that grows in star morphology. My research will add to more understanding to chemotherapy treatment of cancer. Most chemotherapies are toxic to the body because their targeting mechanisms are also present in normal cells. I am investigating potential chemotherapy drugs that may have better targeting against Astrocytoma. These drugs are derived from compounds found in plants. Up to date the exact action of these drugs are unknown. If this mechanism of action of these drugs are known, their targets can be used to refine these drugs to possibly improve their efficiency.

Existing State of Knowledge

The highest grade of glioma is glioblastoma which is the most malignant form of astrocytoma. It has been found that epidermal growth factor receptor expression or overexpression is found in glioblastoma. Some subsets of glioblastoma also have isocitrate dehydrogenase. Diagnostic tests use these markers to evaluate the efficacy of new targeted molecular drugs and for predicting longer survival. Glioblastomas may invade and migrate away from the main tumour within the brain but rarely spread elsewhere in the body. Scientists are currently developing tests that may help identify subcategories of glioblastomas.

Treatment today typically starts with surgery and is followed by radiation, chemotherapy and/or biotherapy. Newly diagnosed glioblastoma patients are given a chemotherapy called Temozolomide with radiation. Temozolomide is an oral drug used to slow or stop the growth of cancer cells in the body. (MedlinePlus) This drug has is an alkylating agent that stops the cells from making new DNA (Cancer Research UK) with a reasonable blood-brain barrier penetration. Many drugs are currently under investigation. Most chemotherapy drugs are either cytotoxic or cytostatic drugs. Cytotoxic drugs destroy tumor cells, and cytostatic drugs alter the behavior of a tumor by changing the tissue in and around the tumor. (American Brain Tumor Association). My work will add to the current cytotoxic chemotherapy drug research for astrocytoma.

Research Question

My project aims to investigate a potential chemotherapy drug for astrocytoma.

Methodology

To investigate potential drugs on astrocytoma, multiple methods will be used. Astrocytoma cells will be cultured and used for many experiments. A WST-1 assay (water-soluble tetrazolium salt) in 2D and 3D will be used to measure the cell’s viability at different drug concentration and combinations. In vivo mouse models will be used to help determine the efficacy of the drug and to see if it is toxic to vital organs. If time permits, an invasion assay will be used to see if the drug slows down or stops cell migration. Western blots may also be used to examine cell death markers.

Your Findings

As of now I have found that the some of the drugs that I am investigating have been effective in 2D and 3D models of glioblastoma. Further investigations will be made into toxicity, mechanism of action and other glioblastoma cell lines.

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Mar 24th, 2:00 PM Mar 24th, 2:50 PM

Anti-Cancer Activity of Synthetic Analogues of Curcumin and Pancreastatin Alone and in Combination with Piperlongumine in Models of Astrocytoma