Treating aggressive breast most cancers with an anti-diabetic drug

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Treating aggressive breast cancer with an anti-diabetic drug

<img src = "https://scx1.b-cdn.net/csz/news/800a/2021/treatingaggr.jpg" alt = "Treatment of aggressive breast cancer with an antidiabetic" title = "Figure shows the effects of gold Metformin drug candidates 3met on aggressive breast tumor growth in vivo. The growth of breast tumors in mouse models from week 1 (before treatment) was shown as a fold change in tumor volume. From week 2 the tumors became palpable and their volume was measured weekly with a vernier caliper. After week 3, no significant tumor growth was observed in a drug treated group (purple color). The chemical structures of metformin and 3met are shown on the left. Recognition: Angewandte Chemie International Edition"width =" 800 "height =" 464 "/>
The figure shows the effects of the gold metformin drug candidate 3met on the aggressive growth of breast tumors in vivo. The growth of breast tumors in mouse models from week 1 (before treatment) was shown as a fold change in tumor volume. From week 2 the tumors became palpable and their volume was measured weekly with a vernier caliper. After week 3, no significant tumor growth was observed in a drug treated group (purple color). The chemical structures of metformin and 3met are shown on the left. Photo credit: Angewandte Chemie International Edition

Researchers at the National University of Singapore developed an approach to combating highly resistant triple negative breast cancers (TNBCs) by interfering with their energy production using cytotoxic gold metformin prodrugs.

Metformin is a widely used "over-the-counter" drug for type 2 diabetes. There is evidence that patients who take metformin for a long time have significantly reduced their risk of developing cancer. Despite well-characterized anti-cancer effects and the low cost of metformin, its use as an anti-cancer agent has serious disadvantages. Metformin is poorly absorbed by the cells. To achieve therapeutic concentrations, it must be taken repeatedly in high doses, which can cause serious side effects in cancer patients.

A research team led by Prof. Ang Wee Han from the Department of Chemistry at the National University of Singapore and Prof. Maria Babak from the City University of Hong Kong developed an approach for chemically conjugated metformin and its analogue phenformin. This is achieved by using an active gold-based molecule fragment to improve bioavailability and create a synergistic effect of the two key components (metformin and gold molecules). By harnessing the electrochemical activity of the gold-based molecule, the team was able to successfully deliver metformin into cancer cells with high selectivity. The anticancer activity of the lead drug candidate developed by the 3met team was more than 6,000 times higher than that of metformin.

Prof. Ang said: "TNBCs represent a particularly dangerous subgroup of breast cancers with the worst prognosis and limited treatment options. This particular aggressiveness of TNBC cells, however, is related to their increased reliance on glucose and lipids, the extra energy needed to maintain a rapid Cancers deliver growth. Since our drug candidates disrupted energy production in cancer cells, we hypothesized that TNBCs might be particularly responsive to such treatment. "

The research team injected the drug candidate into mouse models with breast tumors in the nipple region and monitored the growth of the tumors (see picture). They found that tumor growth in a drug-treated group stopped completely after three weeks, indicating the drug candidate's unique anti-cancer potential. A patent application has been filed for this discovery. The research team is actively developing other effective drugs to treat chemoresistant cancers.

Diabetes drug shows potential in fighting cancer

More information:
Maria V. Babak et al. Impairment of the metabolic profile of triple negative breast cancer using rationally developed metformin prodrugs, Angewandte Chemie International Edition (2021). DOI: 10.1002 / anie.202102266

Provided by
National University of Singapore

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Treating Aggressive Breast Cancer With An Antidiabetic Drug (April 22, 2021)
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