By altering the drug's basic chemical structure, the researchers could create several variations, or analogs, of nimesulide. Nimesulide has been around since 1985, but was banned from clinical and over-the-counter use in the United States due to rare cases of liver damage and related deaths.
"We are working on analogs that will be selective for aromatase expression and also have diminished side effects," Brueggemeier said. "We are obviously in the very early stages of drug discovery with nimesulide analogs, and a long path of preclinical research is needed before we can even begin to think about potential drugs."
The researchers took several of these nimesulide analogs and, in laboratory cultures, tested their effects on estrogen-dependent breast cancer cells taken from human breast tissue. They also tested the analogs on human placental cells to see if the analogs would stop aromatase production in these cells.
The nimesulide analogs stopped aromatase production in the breast cells, but not in the placental cells.
"Aromatase is necessary for normal functions of many tissues in the body," Brueggemeier said. "We still have to test these analogs in other kinds of tissues, however, before we are completely sure that the nimesulide analogs' effects are specific to breast cancer cells."
The analogs prevented a crucial step in the aromatase production process in the breast cancer cells ?they stopped transcription, the first step in gene expression. Compared to other tissues, breast cancer cells use a slightly different signal to indicate when it is time to make more aromatase.
"The pathway leading the aromatase production in breast cancer cells seems to be unique to these diseased cells," Brueggemeier said. "It suggests that aromatase production in other tissues that rely on the enzyme could be spared if a nimesulide analog was take
Source:Ohio State University