Discovery paves the way to prevent multidrug resistance in cancer cells
Researchers find that bitter taste receptors, the same as those on the tongue, play a key role
image: Schematic model of the excretion of incorporated anticancer drugs from ABCB1 via the activation of TAS2Rs. Various anticancer drugs are incorporated into cancer cells, followed by severe cell damage (upper). These incorporated anticancer drugs are recognized by the intracellular TAS2Rs, leading to the enhanced action of ABCB1. The activated ABCB1 promotes the excretion of the drugs, namely reduced accumulation of drugs in the cells, resulting in the contribution to the anticancer drug resistance (lower left). Harmless blockers for TAS2Rs may be used as efficacious agents to attenuate the excretion of the incorporated drugs, leading to an increase in the sensitivity of the cells against anticancer drugs (lower right).
Credit: Okayama University of Science
A research team from the Department of Bioscience, Faculty of Life Sciences, Okayama University of Science, has made a groundbreaking discovery: bitter taste receptors are present inside cancer cells and play a crucial role in pumping anticancer drugs out of the cell—ultimately contributing to the development of multidrug resistance (MDR).
This is the first discovery of its kind in the world. The ancient saying, “Good medicine tastes bitter,” may soon find new scientific relevance in modern molecular biology.
The findings were published online on July 28 in the journal Scientific Reports (Nature Research).
Humans detect bitterness when harmful substances enter the mouth. This happens because bitter taste receptors located in the taste cells of the tongue sense such compounds and trigger an avoidance response that prevents toxins from being swallowed.
Last year, the same research group discovered that identical bitter taste receptors are also present in skin keratinocytes, where they detect toxic substances that penetrate the skin and activate mechanisms that expel them, thereby protecting the body from harm.
In their latest study, the team revealed that the same mechanism operates in cancer cells, such as breast and lung cancer cells. The bitter taste receptors inside these cells detect anticancer drugs and activate a “drug efflux pump” that prevents the drugs from accumulating inside the cell, thereby promoting drug resistance.
Within cancer cells, a variety of bitter taste receptors lie in wait, capable of recognizing numerous anticancer drugs. Once a drug enters the cell, these receptors are activated, triggering the efflux pumps that transport the drug out of the cell.
However, the researchers believe that this mechanism can be reversed. By using specific blockers that inhibit bitter taste receptors, the drug-sensing pathway could be disrupted, potentially preventing the development of resistance (see figure).
Frequent chemotherapy treatments often lead to drug resistance, posing a serious problem in clinical oncology. This study suggests that co-administration of bitter taste receptor blockers with anticancer drugs may offer a solution to overcoming this issue.
While a variety of treatments—including immunotherapy, radiation therapy, and surgery—are used to combat cancer, the researchers hope this discovery will help advance chemotherapy into a new stage of innovation and effectiveness.