Ovarian Cancer Responds to Aspirin Derivative with Chemotherapy

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A new study using ovarian cancer cell lines shows promise in treating the deadly disease by combining the chemotherapy drug cisplatin with an aspirin-like compound to make recurrent cancer cells less resistant to the chemotherapy.

The study appears online in 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 the chemotherapy drug cisplatin. However, cisplatin is not an effective treatment when the ovarian cancer inevitably returns, says Periannan Kuppusamy, a professor of internal medicine at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

"Somehow the ovarian cancer cells adapt and become resistant to this drug,” said Kuppusamy, lead author of the study. “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 somehow be used against the ovarian cancer cells. The study found that the nitric oxide released from the aspirin derivative NCX-4016 reacts with the cellular thiols, which causes the cancer cells to stop proliferating. In addition, the nitric oxide depletes the thiols, making the cancer cells more susceptible to the 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.

Other Ohio State researchers involved in the study are Anna Bratasz, post-doctoral researcher and Nathan M. Weir, research assistant, both in the Davis Heart and Lung Research Institute; Narasimham L. Parinandi, assistant professor of pulmonary/critical care medicine and pharmacology; and Jay L. Zweier, director of the Davis Heart and Lung Research Institute

The National Cancer Institute funded the study.

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