Pot compound seen as tool against cancer

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Marijuana, already shown to reduce pain and nausea in cancer patients, may be promising as a cancer-fighting agent against some of the most aggressive forms of the disease.

A growing body of early research shows a compound found in marijuana – one that does not produce the plant’s psychotropic high – seems to have the ability to “turn off” the activity of a gene responsible for metastasis in breast and other types of cancers.

Two scientists at San Francisco’s California Pacific Medical Center Research Institute first released data five years ago that showed how this compound – called cannabidiol – reduced the aggressiveness of human breast cancer cells in the lab.

Last year, they published a small study that showed it had a similar effect on mice. Now, the researchers are on the cusp of releasing data, also on animals, that expands upon these results, and hope to move forward as soon as possible with human clinical trials.

“The preclinical trial data is very strong, and there’s no toxicity. There’s really a lot of research to move ahead with and to get people excited,” said Sean McAllister, who along with scientist Pierre Desprez, has been studying the active molecules in marijuana – called cannabinoids – as potent inhibitors of metastatic disease for the past decade.

Like many scientific endeavors, connections made between disparate elements – in this case, a plant considered a controlled substance and abnormal cells dividing out of control – involved a high degree of serendipity. The two researchers were seemingly focused on unrelated areas, but found their discoveries pointing in the same direction.

Desprez, who moved to the Bay Area from France for postdoctoral research in the 1990s, was looking at human mammary gland cells and, in particular, the role of a protein called ID-1.

The ID-1 protein is important in embryonic development, after which it essentially turns off and stays off. But when Desprez manipulated cells in the lab to artificially maintain a high level of ID-1 to see if he could stop the secretion of milk, he discovered that these cells began to look and act like cancer cells.

“These cells started to behave really crazy,” Desprez said. “They started to migrate, invade other tissues, to behave like metastatic cells.”

Based on that discovery, he took a look at metastatic cancer cells – not just standard cancer cells, but those responsible for aggressively spreading the disease throughout the body. He found the vast majority tended to express high levels of ID-1, leading him to conclude that ID-1 must play an important role in causing the disease to spread.
Anticancer potential

Meanwhile, McAllister was focused on studying anabolic steroids in drug abuse. McAllister, who also made his way to CPMC from Virginia in the 1990s, became fascinated with the role non-psychotropic cannabidiol, or CBD, interacts with cancer.

Marijuana’s better known cannabinoid – delta-9 tetrahydrocannabinol, or THC – had already shown some anticancer properties in tumors, but the non-psychotropic cannabidiol had largely gone unstudied. McAllister initial research showed CBD had anticancer potential as well.

About eight years ago McAllister heard his colleague, Desprez, give an internal seminar about his work on ID-1, the manipulated protein cells that masquerade as cancer cells, and metastases. That produced an idea: How effective would cannabidiol be on targeting metastatic cancer cells?

The pair teamed up – Desprez with his apparently cancer-causing ID-1 and McAllister with his cancer-fighting CBD – deciding to concentrate their research on metastatic cells of a particularly aggressive form of breast cancer called “triple negative.” It is so named because this type of breast cancer lacks the three hormone receptors that some of the most successful therapies target. About 15 percent of breast cancers fall into this category, and these cells happen to have high levels of ID-1.

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