Researchers at the University of Warwick report that when the sodium formate is used in combination with a metal-based cancer treatment it can greatly increase its ability to shut down cancer cells. Developed by the university’s department of chemistry, the drug, a compound of the metal ruthenium called JS07, is capable of exploiting a cancer cell's natural weaknesses and disrupts its energy generation mechanism.
Laboratory tests on ovarian cancer cells have shown that when used in combination with sodium formate JS07 is 50 times more effective than when acting alone. Derived from formic acid, which is commonly found in a number of natural organisms including nettles and ants, sodium formate (E-237) is more commonly used as a food preservative.
The Warwick researchers, in a study (“Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design”) published in Nature Communications, developed a novel method for binding sodium formate with JS07 to form a more potent form of the drug. The scientists subsequently found that the potent form of JS07 acts as a catalyst when it interacts with a cancer cell's energy-generating mechanism. This interaction disrupts the mechanism, causing the cell's vital processes to cease functioning and for the cell to shut down.
“In this work, we have shown for the first time that Noyori-type catalytic transfer hydrogenation can be achieved in living cells, using RuII arene complexes with a chelated sulfonylethylamine ligand and formate as the hydride donor to convert coenzyme NAD+ into NADH, and thereby modulate the NAD+/NADH redox couple,” wrote the investigators.
“Cancer cells require a complex balance of processes to survive. When this balance is disrupted the cell is unable to function due to a range of process failures and eventually shuts down,” explained Peter Sadler, Ph.D. “The potent form of JS07 has proven to be very successful when tested on ovarian cancer cells”.
According to Dr. Sadler, the combination of sodium formate and JS07 provides a number of potential benefits to cancer patients, including a reduction in the negative side-effects compared with other traditional cancer treatments:
“By itself, JS07 is capable of shutting down cancer cells but when used in combination with sodium formate this ability is significantly increased. As a result, lower doses would be required to target cancer cells, reducing both the drug's toxicity and potential side-effects,” he continued.
A further benefit is that once the potent form of JS07 has interacted with a cell's energy generation mechanism the remaining non-potent JS07 molecules can then be reused in combination with a fresh supply of sodium formate.
The research might also lead to substantial improvements in cancer survival rates.
“Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK,” noted Isolda Romero-Canelon, Ph.D. “It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells”.