A team of researchers led by Prof ANG Wee Han from the Department of Chemistry, National University of Singapore and Prof Maria BABAK from City University of Hong Kong devised an approach to chemically conjugate metformin (a widely prescribed “over-the-counter” medication for Type 2 diabetes), as well as its analogue phenformin. This is achieved by using a gold-based active molecular fragment to improve bioavailability and to achieve synergistic action of the two key components (metformin and gold molecules). By taking advantage of the electrochemical activity of the gold-based molecule, the team successfully delivered metformin into cancer cells with high selectivity. The anticancer activity of the lead drug candidate developed by the team named 3met, was found to be more than 6,000 times higher when compared to metformin.
Prof Ang said, “TNBCs represent an especially dangerous subset of breast cancers with the poorest prognosis and limited treatment options. However, this particular aggressiveness of TNBC cells is related to their increased dependence on glucose and lipids, which provide additional energy to sustain rapid cancer growth. Since our drug candidates interfered with energy production in the cancer cells, we hypothesised that TNBCs might be particularly responsive to such treatment.”
The research team injected the drug candidate into murine models having breast tumours at their nipple region and monitored the growth of the tumours (see Figure). They found that the growth of tumours in a drug-treated group completely stopped after three weeks, indicating the unique anticancer potential of the drug candidate. A patent application has been filed on this discovery. The research team is actively working on the development of other efficient drugs for the treatment of chemo-resistant cancers.
The figure above shows the effects of gold-metformin drug candidate 3met on aggressive breast tumour growth in vivo. Growth of breast tumours in murine models from week 1 (before treatment) presented as a fold change in tumour volume. Starting from week 2, the tumours became palpable and their volume was measured using calipers on a weekly basis. No significant tumour growth was observed after week 3 in a drug-treated group (purple colour). Chemical structures of metformin and 3met are given on the left. [Credit: Angewandte Chemie International Edition]. Read more on their discovery here.
