Combining cisplatin with an aspirin derivative restores sensitivity to chemotherapy in cisplatin-resistant ovarian cancer cell lines, according to an article published online February 23rd by the Proceedings of the National Academy of Sciences.

As a first course of treatment, ovarian cancer typically is treated with surgery followed by a regimen of cisplatin. However, cisplatin is not an effective when the ovarian cancer inevitably returns, said Periannan Kuppusamy, MD, lead author of the study: “Somehow the ovarian cancer cells adapt and become resistant to this drug. Once treated with cisplatin, the ovarian cancer cells develop an abundance of thiols, which are a kind of cellular antioxidants that protect the cancer from the chemotherapy.”

Kuppusamy wondered whether the abundance of thiols could be used against the ovarian cancer cells. In the current study, he found that the nitric oxide released from the aspirin derivative NCX-4016 reacts with the cellular thiols, causing the cancer cells to stop proliferating. In addition, the nitric oxide depletes the thiols, making the cancer cells more susceptible to chemotherapy.

“The nitric oxide-releasing ability of the aspirin derivative NCX-4016 is enhanced by thiols, so I thought this type of treatment might work better in a tumor cancer cell that is rich in thiols, such as a resistant ovarian cancer,” Kuppusamy said.
Kuppusamy plans to continue this research in animal models.

He collaborated with Dr. Louis Ignarro of the University of California School of Medicine in Los Angeles, who along with two colleagues won the 1998 Nobel Prize for Physiology or Medicine for their work in discovering the biologic role of nitric oxide.