Objective
The global incidence of colorectal cancer is the third
highest and is the fourth leading cause of cancer related death. Despite advances
in treatment options, chemotherapeutic resistance presents as one of the main
challenges faced by patients, making the development of novel therapeutic
options urgently required. Greater efficacy in chemotherapeutic compounds is
also required to reduce the amount of tissue currently surgically removed from
these patients.
It has been demonstrated that animal venom provides a rich
library of potential novel therapeutics and is an excellent source of drug
discovery tools. This research focussed on developing a cytotoxin based Targeted
Venom Discovery Array™ (T-VDACTX) to provide a library of potential drug-like
molecules. This library of venom components was then screened against
colorectal cancer cells and cell viability measured.
Five previously screened cobra venoms were separated by
two-dimension (2D) High Performance Liquid Chromatography (HPLC) using ion
exchange chromatography as the first dimension and reverse phase HPLC as the
second dimension. 303 2D fractions were collected and plated into 96-well
format and screened for cell viability against SW620 colorectal cancer cells.
These venoms had already shown selectivity between different cancer cell types.
12 of the T-VDACTX fractions were found to have
activity against SW620 cells (representing a 3.9% hit rate) at a dose of 0.5 µg
per well. This poster presents a proportion of this data in detail as an example
of the utility of these compounds. The activity of three ‘hit’ fractions from
two cobra species against SW620 cells will be explained.
