Scientists Uncover Pathway To Cancer-Fighting Compound Found In Madagascan Plant

The Madagascan periwinkle makes a cancer-fighting drug, and we now know exactly how. Andrew Davis

Scientists have finally figured out how a naturally occurring cancer-fighting chemical is made, after over 60 years of being used to treat patients.

Derived from the Madagascan periwinkle, the compound vinblastine is one of the safest and most effective medicines used to treat a wide range of cancers – from Hodgkin’s lymphoma to lung cancer to brain cancer – by preventing the cells from dividing. But until now, researchers have not fully understood how the plant is able to make such an incredibly important drug. The research is published in the journal Science.

The compound was originally isolated in 1958, but obtaining it from the plant itself is incredibly inefficient and therefore costly. It takes around 500 kilograms (1,100 pounds) of dried periwinkle leaves to make just a single gram of vinblastine. For this reason, many researchers have been trying to come up with more effective ways to synthesize the drug in the laboratory.

For the last 15 years, a team of scientists at the John Innes Centre have been working hard to figure out which genes in the plant produce the enzymes necessary to make it. Now, they have finally uncovered the last piece of the puzzle.

“Vinblastine is one of the most structurally complex medicinally active natural products in plants – which is why so many people in the last 60 years have been trying to get where we have got to in this study,” explains Professor Sarah O’Connor, head of the laboratory that has helped unravel the mechanism, in a statement. “I cannot believe we are finally here.”

Their end result – which builds on the work of countless other researchers at other institutions around the world – reveals the complex pathway through which the plant makes the vital drug. They have counted no less than 31 steps that take it from the primary chemical precursor all the way through to the active vinblastine.

They now want to be able to use this to try to synthesize microgram quantities of vinblastine, or potentially one of its two precursors known as vindoline and catharanthine, over the next year and a half. The end goal is to try to bump up production of the drug.

“With this information we can now try to increase the amount of vinblastine produced either in the plant, or by placing synthetic genes into hosts such as yeast or [other] plants,” says Professor O’Connor.

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