MTSU Researchers Take Aim at Metastatic Breast Cancer

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

New hope for a low-toxic treatment of this cancer has been reported in the prestigious research journals Scientific Reports and Oncotarget.

Lead researcher Iris Gao with the Tennessee Center for Botanical Medicine Research reports the isolation and identification of a new, patented compound, DMDD, from the root of the tropical star fruit tree, is helping treat this form of cancer.

“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 reveal metastatic tumors resulting from late-stage breast cancers are usually inaccessible by surgery or radiotherapy. Consequently, there are no effective treatments. An alarming 90 percent of cases at stage IV or later result in death.

Gao said the research began in 2011 when the Tennessee Center for Botanical Medicine Research was founded at MTSU, and the university — along with a grant from Tennessee-based Greenway Herbal Products, has made a significant investment in the center to make the research findings possible.

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

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

The acronym 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 DMDD significantly extended the life span of breast tumor-bearing mice, shrinking not only the primary breast tumor, but most importantly inhibiting the metastasis, or spread, of the breast tumor to the lung and liver, according to the Scientific Reports article published July 27.

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

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

“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.”

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

The researcher, who is a member of the School of Agribusiness and Agriscience faculty, also reported the lack of toxicity of DMDD in mice and normal human cells.

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 anticancer 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 could be used as an anticancer agent against breast cancer.

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