Researchers Show Curcumin Protects Against Chemoresistant Pancreatic Cancer Through lncRNA

Curcumin is known for its powerful anti-inflammatory and antioxidant benefits, but a new study by researchers at Baylor Scott & White Research Institute reveals an additional benefit: its potential to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC), a common but aggressive form of cancer in the pancreas.

The study, “Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression,” recently was published in Carcinogenesis, an integrative cancer research journal. Previous research demonstrated the advantages of taking curcumin preventatively, but this is the first study of its kind to demonstrate benefits of curcumin as an adjunct to chemotherapy.

Resistance to chemotherapeutic drugs is a major challenge in caring for patients with PDAC, the fourth leading cause of cancer-related U.S. deaths. Patients may respond to chemotherapy initially, but as cancer stem cells form, the body can develop drug resistance. Now, researchers have developed an improved understanding of the molecular events underlying the development of pancreatic stem cells and the role that curcumin—the main component of turmeric—plays in overcoming resistance to vital chemotherapy drugs.

“By treating certain cells with small doses of curcumin, we were able to reverse the pathways that lead to chemoresistance,” says Ajay Goel, Ph.D., director of gastrointestinal research and translational genomics and oncology at Baylor Scott & White Research Institute and author of the study. “This is an important breakthrough that could lead to better prognosis and longer lives for patients with chemoresistant pancreatic cancer.”

Dr. Goel and his team identified Enhancer of Zeste Homolog-2 (EZH2) subunit of Polycomb Repressive Complex 2 (PRC2) as key players in regulating drug resistance. When pancreatic cancer cells were treated with curcumin, the pathways associated with chemotherapy drug resistance were inhibited, thereby increasing reception to first-line drug therapy. Curcumin also was found to prevent the formation of spheroids, a hallmark of cancer stem cells, which would in turn reduce tumor growth and recurrence.

Curcumin enhances sensitivity to gemcitabine in GemR cells in vivo

lncRNA

(A) The timeline for generation of xenograft model in athymic mice and the treatment groups. Blue arrows—gemcitabine injections, red arrows—curcumin injections. (B) Progressive tumor volume increase with treatments. (C) (right) final tumor weight (left) an image of xenograft tumors. (D) qRT-PCR analysis of PVT1 expression levels in tumors from the different treatment groups. (E) Schematic of the mechanism of how curcumin sensitizes gemcitabine and decreasing cancer stemness through attenuation of expression of the PRC2 complex and the lncRNA PVT1. 

Other studies have demonstrated curcumin’s role in mitigating a variety of health conditions, including arthritis, depression and various types of cancers. Dr. Goel’s research team is leading the way in multi-faceted studies to explore the healing powers of this natural compound. Current clinical trials are underway to explore the role of curcumin and cervical, breast and colorectal cancers.

“Food-based botanicals have the potential to restore a healthier gene expression in patients but without the toxicity of certain drugs,” Dr. Goel said.

Yoshida K, Toden S, Ravindranathan P, Han H, Goel A. (2017) Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression. Carcinogenesis [Epub ahead of print]. [abstract]

Source – Baylor Scott & White Health

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