2011 Postgraduate Research Competition - UNSW Science - The ...

Page |45
The Potential of Anti-Psychotics and
Statins as Chemotherapeutics
Nirmani Wijenayake G and Louise Lutze-Mann
School of Biotechnology & Biomolecular Sciences
Abstract
Glioblastoma Multiforme (GBM) is a malignant form of cancer that is difficult to treat. The
median survival of a patient with GBM is only 1 year. In most cases, surgical resection is
usually followed by radiotherapy and chemotherapy with Temozolomide, one of the
approved drugs for the treatment of GBM. Unfortunately, large number of patients develop
resistance against Temozolomide and other chemotherapeutics are unavailable for
treatment due to their inability to cross the blood brain barrier. Therefore, there is a need for
new potential chemotherapeutics against GBM.
Meta-analysis of cancer in schizophrenic patients suggests a lower incidence of some
cancers leading to the hypothesis that antipsychotic drugs taken regularly by these patients
may have the ability to act as chemotherapeutics. We have demonstrated the significant
effect of number of antipsychotics in vitro with the use of short term cell viability assays and
long term clonogenic assays. Previous studies indicated that cytotoxic effects of
antipsychotic drugs maybe due to blockage of intracellular trafficking of exogenous and
endogenous cholesterol. We have demonstrated the ability of lipophilic, cholesterol lowering
statins to induce GBM cell death in vitro. By combining antipsychotics with statins, we have
demonstrated an increased cytotoxicity of antipsychotics.
Our results established antipsychotics and statins as potential chemotherapeutic agents
against GBM. The IC50 and LD50 values for these drugs are smaller and far superior
compared to the current treatment, Temozolomide, increasing their value in the treatment of
GBM.
Abstract
Restoring Access to Embellistatin
Justin Nash and Jonathan Morris
School of Chemistry
Cancer is a major cause of death worldwide and it is characterised by uncontrolled rapid
cell growth. Disruption of cancer can be achieved by the use of drugs which can selectively
target and inhibit processes vital to the growth of cells.
Microtubules are an established target for treatment as they are involved in many aspects of
cell growth and are vital for the growth of new blood vessels. While treatments targeting
these biological processes have been developed, there is an ever evolving resistance to
current drugs and a need for a more active and selective therapeutic.
The natural product embellistatin represents a promising step forward as it targets both
microtubules and angiogenesis. This compound is no longer available from its natural source,
which has stymied progress. We are developing a total synthesis which will allow us to
prepare the compound from readily available materials. By restoring access to this important
molecule, we will be able to develop it as a new therapeutic agent.
| science + society