Middle Tennessee State University faculty, students and funding are playing a crucial role in breakthrough research aimed at helping treat metastatic breast cancer.

Lead researcher Iris Gao with the Tennessee Center for Botanical Medicine Research says the team has isolated and identified a new, patented compound, DMDD, from the root of the tropical star fruit tree, that is helping treat this form of cancer.

This new hope for a low-toxicity treatment for metastatic breast cancer has been reported in the prestigious research journals Scientific Reports and Oncotarget.

Lead researcher Iris Gao, left, and graduate student Nadin Almosnid document their findings on metastatic breast cancer cells in the tissue culture teaching lab inside the MTSU Science Building. (MTSU photo by J. Intintoli)

“Continued research will lay a foundation for developing this as an anti-breast cancer drug,” Gao said.

MTSU graduate students, a visiting Chinese scholar, and partner Guangxi Medical University in Guangxi, China, are aiding in the effort.

Their findings note that metastatic tumors, or those that have spread to other organs, resulting from late-stage breast cancers are usually inaccessible by surgery or radiotherapy. That means there are no effective treatments, and 90 percent of cases at stage IV are fatal.

MTSU has made a major investment in the Tennessee Center for Botanical Medicine Research to find a cure for metastatic breast cancer since the center’s founding in 2011. A grant provided by Tennessee-based Greenway Herbal Products has assisted the center’s overall research efforts since 2016.

The center and Guangxi Botanical Garden of Medicinal Plants in Nanning, China, which have an exclusive collaborative agreement, developed a novel approach to accelerate development of Western medicines from botanical extracts based on their respective strengths and expertise.

The Guangxi garden holds the largest depository of plants used in traditional medicine, including the tropical star fruit tree.

MTSU graduate student Gheda Alsaif, foreground, and visiting Chinese scholar Li Chen take a culture of the human vascular cells in the MTSU Science Building tissue culture teaching lab. (MTSU photo by J. Intintoli)

“So far, our cancer research has resulted in 16 research articles in scientific journals and three patents on potential cancer therapeutics,” said Gao,  author and inventor of the provisional international patent filed for DMDD in 2015.

The initialism DMDD comes from the lengthy compound 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione from the root of the tropical star fruit tree.

Working with Guangxi, the joint studies “… indicate that DMDD (the agent) has significant potential as a safe and efficient therapeutic agent to treat metastatic breast cancer,” Gao said.

“As metastatic breast cancer is such a devastating disease, it is essential to develop new, less toxic therapeutic agents to prevent and treat this cancer,” Gao said. “In contrast to toxic synthetic chemicals, medicinal plants have provided us an interesting alternative to develop efficacious and affordable anticancer drugs.”

“We are excited to observe the potent anti-cancer efficacy as well as the low toxicity of DMDD in both human cells and mice, and we will continue to study the anti-cancer potentials of DMDD and its underlying mechanisms,” she added.

Researchers from both universities demonstrated that DMDD significantly extended the life span of mice with breast tumors, shrinking not only the primary tumor but most importantly inhibiting the spread of the breast tumor to the lung and liver, according to this summer’s Scientific Reports article.

The researchers also reported the lack of toxicity of DMDD in mice and normal human cells.

Before this publication, the Gao-led team — which includes grad students Nadin Almosnid and Hyo Sim Park — showed that DMDD suppressed a variety of human cancer cells, including breast, lung and bone cancer cells. This earlier work was published in the 2015 Oncotarget article.

Grad student Gheda Alsaif and visiting Chinese scholar Li Chen recently joined the team. Deborah Knott, a master’s degree student, and Amy Ridings, a University Honors College undergraduate, also have been involved in the cancer research; Gao also is their mentor for their dissertation research.

Visiting Chinese scholar Li Chen, left, assists as lead researcher Iris Gao prepares a sample of DMDD powder to make the solution used in breast cancer research at MTSU. (MTSU photo by J. Intintoli)

Chen has been a part of the collaboration and exchange with China, Gao added.

“All of the graduate and undergraduate students have been the co-author of my publications and/or conference proceedings,” Gao said. “These students are fantastic, and I enjoy working with them.”

Gao said the star fruit tree is native to and widely distributed in Southeast Asia. The root of the tree has been used in traditional Chinese medicine to treat debilitating headaches for thousands of years.

The consecutive discoveries of this plant-derived anti-cancer agent have resulted from the collaboration between Gao and Dr. Renbin Huang at Guangxi Medical University. The partnership was established in 2013 when Gao first visited Huang’s research lab at GMU. Huang’s lab has previously studied DMDD as a robust anti-diabetic agent, Gao said.

Inspired by recent studies linking diabetes and breast cancer and fascinated by the fact one of the world’s top anti-diabetic drugs, metformin, can effectively treat breast cancer, Gao decided to investigate whether DMDD also could be used to fight breast cancer.

“The research has updated the knowledge of DMDD and provided new insights into its potential as a cancer drug,” Gao said.

To learn more about the botanical medicine research center, visit www.mtsu.edu/tcbmr.

— Randy Weiler (Randy.Weiler@mtsu.edu)

MTSU breast cancer lead researcher Iris Gao holds the bottle of the DMDD compound used in the MTSU lab. (MTSU photo by J. Intintoli)