A Better Way

Researcher Discovers the Humble Sweet Potato Plant May Lead to Kinder, Gentler Ways to Fight Cancer

Ritu Aneja is a scientist who lives off the beaten research path. While Aneja's focus has been and continues to be research in mitosis — the process of cell division — the fight against cancer is her endgame. "There has been a lot of progress in our understanding of how cells behave and the pathogenesis of cancer, but we really don't know how to find the magic bullet," says Aneja, an associate professor of biology, whose lab in the Petit Science Center explores natural ways to find a "kinder chemotherapy."

Since scientists first discovered decades ago that certain chemicals administered in combination can cure some cancers, there have been numerous advances that have improved the effectiveness of chemotherapy.

However, most drugs that kill the unruly cancerous cells are often indiscriminate and also kill healthy tissues. Many are often so toxic that they also place the health care professionals handling them at risk, too. Finally, the drugs often can't completely stop cancer cells from proliferating.

Indeed, there may be no magic bullet — no single chemical compound that will be the sole answer to successfully treating cancer. But Aneja and her lab are working on a natural way that brings multiple compounds to the table that work together to kill cancerous cells and prevent their proliferation — all the while serving as a treatment that is much safer to patients and their caregivers.

Aneja has discovered through an unlikely source that a plant eaten for centuries by different cultures around the world might just provide the answer: the leafy greens of the sweet potato plant.

The Natural

Scientists can spend years in the lab looking for cures and diagnostics for diseases, using chemical compounds synthesized in labs. But out in the hospitals and clinics of the world, many of the drugs used to treat disease have their origin in nature.

"Many drugs have come from plants, and even the best cancer drugs in the clinic are from plants," Aneja says.

Two of the most effective anti-cancer drugs come from plants. Vinblastine from Vinca rosea, a type of periwinkle, is used to treat Hodgkin's lymphoma, lung cancer, breast cancer and testicular cancer. Paclitaxel, derived from the bark of the Pacific yew tree, is used to treat patients with lung, ovarian and breast cancer.

"For thousands of years, we've treated ourselves with folklore medicine, and even today, everything is based on that. There's a lot of strength and wealth in nature," Aneja says.

In discovering the anti-cancer properties of sweet potato greens, Aneja turned to traditional Japanese literature. From there, she learned about the health benefits of the plant. High in polyphenols, Vitamin B, beta carotene, iron, calcium and zinc, the greens' nutritional richness make them a prime candidate for study.

Commonly eaten in West Africa and in Asia — specifically in Taiwan and mainland China — the greens have been called a "poor man's food." Here, they are typically cut back before the sweet potatoes are dug up and harvested.

Aneja had a hunch that there was something more to the humble green.

Consulting with colleagues at Tuskegee University in south Alabama who research the cardiovascular benefits of sweet potatoes, Aneja began to learn more about the crop.

At that time, Aneja started research with not only the leafy greens of the sweet potato, but also the peel. While the peel didn't show superior cancer-fighting properties, the greens would prove to host a bounty of the right compounds to kill cancer.

Nature's Workers Other Georgia State professors are working on natural ways to detect and fight disease. They include: PENG GEORGE WANG, a Georgia Research Alliance Eminent Scholar and professor in chemical glycobiology, who is investigating carbohydrate-based natural products to develop new ways to diagnose and treat diseases. One research focus looks at carbohydrates called human milk oligosaccharides, found in human breast milk. The oligosaccharides have been shown to counter bacterial infections, and Wang wants to learn more about how to produce these compounds on a larger scale in order to create better drugs against infection. SURI IYER, associate professor of chemistry, who is also using carbohydrates to counter disease. His lab is looking to understand how toxins and pathogens recognize certain types of carbohydrates to bind and infect cells. JIAN-DONG LI, director of the Center for Inflammation, Immunity and Infection (CIII) and Georgia Research Alliance Eminent Scholar, who examines a drug called Vinpocetine, which is based on chemicals found in the periwinkle plant, and its anti-inflammatory effects. The drug has been used in Europe, Japan and China for neurological conditions, and is non-toxic. Since the drug has already been proven to be non-toxic, it can be more quickly "repositioned" for use against inflammation. NICOLE LOPANIK, an assistant professor of biology, who is interested in the production of natural compounds — including one called bryostatins — produced by marine organisms. The chemicals may have anti-cancer and neurological impacts.

The Critical Fraction

Aneja and research scientist Prasanthi Karna, formerly at Georgia State, immediately started work with sweet potato green extract on prostate cancer cells grown in test tubes — known as "in vitro" research.

Prostate cancer cells are ideal for evaluating a prospective cancer treatment because they are relatively slow-growing — giving Aneja's lab a better window to examine the greens' anti-cancer properties.

Aneja couldn't believe the results. They applied the extract to prostate cancer cells in petri dishes to see if the extract could kill the cells and inhibit their growth. In total, the sweet potato greens showed a 69 percent efficacy in inhibiting prostate tumor growth as compared to controls in the experiments.

"I asked Sushma to [repeat the experiment] several times to make sure," she says.

The whole extract proved to be effective against the prostate cancer cells, and Aneja wanted to publish the new knowledge. But journal editors demanded to know more about what was in sweet potato greens that caused their effectiveness.

"What these journals would ask us all the time is 'Tell us something — what's in there? What is in the extract and what is the nature of the compounds?'" Aneja says.

So the lab dived into breaking down the extract. Sushma Gundala is now the main researcher in Aneja's lab investigating the greens and continuing the work started by Karna.

Gundala broke down the extract using a separation process called "fractionation," where mixtures of solids, liquids or suspensions are divided into smaller parts. Using a further separation process called chromato-graphy, the lab separated the whole extract into 17 fractions of compounds and investigated the traits of each.

"To reduce the burden of working with 17, we brought down the number to seven," Gundala said. "Nevertheless, it has been a daunting task to fractionate sweet potato green extract due to processing difficulties as our approach was to not just look at the parts, but to link them to activity."

The fraction that showed the most anti-cancer activity is what Aneja and her lab call "Fraction 5." The fraction is very powerful and is effective in very tiny amounts — nanograms per milliliter — unlike the other fractions.

The lab has identified at least two specific compounds within Fraction 5 — caffeic acid and chlorogenic acid — but the others remain a mystery. The most meaningful finding to Aneja's lab is that all of the compounds work together to fight cancer.

Her lab separated Fraction 5 further into subfractions to see if they could isolate other components responsible for Fraction 5's total anti-cancer activity, but none of the subfractions were as active as Fraction 5 as a whole.

"That's when we decided to stick with Fraction 5 and characterize it further rather than individualizing a single component, because it was clear that there was no activity there," Gundala says.

How does Fraction 5 work? Put simply, they're not sure. The ratios of the compounds within Fraction 5 hold importance, but other aspects are unknown. That's a future direction Gundala and Aneja are working on.

There are a number of possibilities as to how the fraction's compounds work, and there are multiple issues to sort out — pharmacokinetics, or what the body does to the compounds, and bioavailability, the degree to which a substance becomes available to the target tissue.

The fraction also proved to be harmless to healthy cells.

Toward a Kinder, Healthier Future

There are many directions Aneja's lab can take, including research on a different, deadlier and faster-growing cancer — pancreatic cancer, which has one of the lowest five-year survival rates and spreads very quickly.

"It's a very deadly cancer, and there are not many people working on it," Aneja says. "There are not many drugs available either. If the greens show even a little bit of protection, it will be a great leap."

To continue her work, she was awarded a $720,000 grant from the American Cancer Society — the third such grant for the GSU Department of Biology.

Perseverance on the research path may yield tangible results, going from the lab bench into the public sphere, and one tangible result of the sweet potato green research might be a dietary supplement for cancer prevention, Aneja says. Results could also lead to better cancer treatments in a clinical setting.

That day may come sooner rather than later. Aneja is constantly striving for the next discovery, as well as seeking other projects along the same lines that investigate natural ways to kill and prevent cancer. One promising project has examined the cancer-fighting abilities of an extract from whole ginger root, which has also shown efficacy against cancer.

"If only I had 48 hours in a day instead of 24," Aneja says with a smile. "And I have a lot of help from my grad students. They work very hard and have matured so much along the way."

Her students, like Gundala, are the engines that help keep her lab going. And Aneja, who is passionate about seeking new opportunities to expand knowledge that can lead to better treatments, is happy to set their motivations alight.

"I have to infuse a passion," she says. "When they work with me, they have to be fired up. I have to show them the direction and the path, but then I give them a lot of freedom. Sometimes they have one crazy idea — and it turns into a new direction for discovery."