topotecan | New Under The Sun Blog

I know we’re only four days into February, but it has been packed full of celebrations- Groundhog Day, the Superbowl, and National Carrot Cake Day (Yes, it’s a real thing.*). Today, February 4^th is World Cancer Day. Now, I know what you are thinking. “I come here for the plants. She only writes about plants, photosynthetic organisms and autotrophic wannabes.” What do plants have to do with cancer? Do plants get cancer? Not exactly. Sometimes they get galls or weird growths, but it’s not the same as mammalian cancer. It’s a good thing that plants don’t get cancer at the same incidence rates as modern humans or we’d all starve to death before we could even get cancer. Is this going to be a post about plant-based diets and cancer remedies? Wrong again- although it is probably a good idea for lots of reasons to eat a variety of whole fruits and vegetables every day.

So, you ask again, “What do plants have to do with cancer?” Here it is- A number of chemotherapy drugs are actually plant-derived chemicals. They may look anything-but-natural when you think about the sterile clear liquids that must slowly drip through plastic tubing and into medi-ports. Yet, before they were FDA-approved and mass-produced, these molecules existed in plants, relegated to the catch-all category termed ‘secondary metabolites’. At some point scientists discovered their anti-cancer properties and studied them further for clinical applications. To prevent the over-exploitation of the plant species that produce these compounds, many are now produced synthetically using advanced organic chemistry or semi-synthetically from abundant plant precursors. Some ‘natural’ molecules may have shown initial promise until further clinical experiments showed unacceptable toxicity or side-effects. Some of these cases still yielded useable chemotherapy agents, but as synthetic derivatives with slightly altered chemical structures. Nevertheless, natural products from plants are the source of inspiration for a number of effective cancer treatments today. You can bet there are more to come in the research pipeline.

Taxol (Paclitaxel): This chemical was discovered in a screen of natural products for anti-cancer properties. It was extracted from the bark of the Pacific yew tree (Taxus brevifolia). It took scientists a couple more decades to figure out its total synthesis. Even now, the total synthetic route is not economically feasible. Of course, pillaging the forests for Pacific yew trees isn’t sustainable either. Taxol is currently manufactured using a plant cell fermentation system of yew plant cells along with fungal cells to mass produce the chemical. Taxol is used to treat lung, ovarian and breast cancers.

Hycamtin (Topotecan): Topotecan is a semi-synthetic derivative of campothectin, which is a natural product of Campotheca acuminate (aka the Happy Tree or Tree of Life). While campothectin showed effective anti-cancer properties, it did not dissolve readily in water and gave adverse side effects in clinical trials. With a few modifications of the chemical structure, Topotecan reduced these negative characteristics. It is used to treat lung, ovarian and cervical cancers.

VP-16 (Etoposide) and Vumon (Teniposide): These drugs are derivatives of podophyllotoxin produced in the May Apple (Podophyllum peltatum). The natural product podophyllotoxin is used in topical creams to treat genital warts caused by the human papilloma virus, but only derivatives with modified structures are effective anti-tumor agents. These drugs are used to treat leukemia, lymphoma, lung cancer and testicular cancer.

Oncovin (Vincristine) and Vinblastine: Vincristine and Vinblastine are natural products of the Madagascar periwinkle (Catharanthus roseus, formerly known as Vinca roseus). These molecules are used to treat lymphoma, Hodgkin’s lymphoma, and leukemia.

Chemotherapy drugs and their plant origins. All pictures via Wikipedia

Celebrate World Cancer Day by learning something new.** Find out how you can reduce your cancer risk. Learn how you can help in your community- support doctors, patients, caregivers, and researchers. The American Cancer Society is a good place to start. Tell a survivor how much they inspire you. Let Chevrolet “Purple your Profile” and get them to donate $1 to the American Cancer Society. Finally, appreciate the biochemical prowess of plants and the persistence of their researchers that make these treatments possible.

Johnna

*So say the people that eat carrot cake on February 3. Missed it? Mark your calendar for next year.

**Hopefully this blog post has already accomplished that. Check!

References and Links:

http://www.sciencedirect.com/science/article/pii/S0378874105003259

http://www.sciencedirect.com/science/article/pii/S0006295296006545

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614754/

http://en.wikipedia.org/wiki/Topotecan

http://en.wikipedia.org/wiki/Etoposide

http://en.wikipedia.org/wiki/Teniposide

http://en.wikipedia.org/wiki/Vincristine

http://en.wikipedia.org/wiki/Paclitaxel