Old Drug A New Hope For Cancer WSU Pharmacologist Finds Way To Use Chinese Remedy

A Washington State University researcher working with a once-abandoned Chinese cancer remedy says recent tests show the drug holds remarkable promise against breast and skin cancer.

The National Cancer Institute 25 years ago wrote off camptothecin as “ineffective.” But after developing a way to inject the drug without it being destroyed by the body, WSU pharmacologist Sayed Daoud found it was 100 percent effective in killing certain breast cancers and melanoma in animals.

“This drug is more or less like taxol,” Daoud, 38, said, referring to the anti-cancer chemical found in Pacific yew trees. “I feel like it is one of the promising drugs that we’re going to have because of the broad spectrum of activity … against various types of cancer.”

Camptothecin, an extract of the plant Camptotheca acuminata, was used for decades in China as an oral remedy for stomach cancer before being brought to the United States in 1970 by the NCI’s Experimental Therapeutic Program. But when it was administered in injectable form here, the drug proved to be toxic, causing liver damage and hemorrhaging.

Five years ago, Beppino Giovanella, a colleague of Daoud’s at St. Joseph’s Hospital in Houston, was inspired to do more research on the drug when he saw its oral version was indeed effective against stomach cancer.

Giovanella and Daoud also concluded the drug preferred an acid environment, which explained why it could withstand ingestion into the stomach. Injecting the drug into the slightly alkaline pH of the body destroyed a protective “closed-ring” structure around the drug molecule, rendering it ineffective, if not poisonous.

Enlisted by Giovanella, Daoud set out to make a version of the drug that could be injected and thereby put to use against a wider range of cancers. Working in Houston and then at WSU, where he arrived in 1991, Daoud developed small fatty globules called liposomes that could carry the drug to a cancer cell without opening the protective ring.

“That globule will act as a shielding environment from the body,” he said, “and at the same time also act as a carrier. It takes the drug to where you want.”

After eight months of work, Daoud found a globule that could stay stable in the body long enough to release a constant dose of the drug over time. He then began looking at whether the drug worked.

Essentially, the drug slows a tumor’s ability to reproduce.

Because cancer cells reproduce so quickly, they must create huge amounts of DNA the cell’s genetic carrier. To fit inside the cell’s nucleus, the DNA strands twist and overlap each other, interlocking in small nicks made and resealed by a special enzyme, topoisomerase.

Camptothecin keeps the topoisomerase from working, destroying the DNA’s and the cancer’s - ability to reproduce, Daoud said.

“If you prevent the formation of DNA, obviously you are not going to form more cells,” he said. “The cells will die.”

Unlike conventional chemotherapy, the drug also disrupts cancer cells more than normal cells because they have far greater amounts of topoisomerase.

Earlier this year, Daoud, Giovanella and a researcher in Cairo published results of work that showed the drug killed breast cancers and melanoma tumors in mice to which human tissue had been grafted. Other work by Giovanella showed good results against colon cancer and leukemia, Daoud said.

This June, Daoud began a two-year, $105,000 project to develop a version of the drug that could then be used in clinical trials on humans.

If the trials are successful, the drug could be available to the public in five years.

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