New Compound Developed from Plant-Derived Nicolaioidesin C Enhances Chemotherapy Effectiveness in Pancreatic Cancer
Summary
A research group led by Associate Professor Suresh Awale of the Institute of Natural Medicine, University of Toyama, in collaboration with Professor Naoki Toyooka and Assistant Professor Takuya Okada of the Faculty of Engineering, and Professor Tsutomu Fujii of the Faculty of Medicine, has developed a promising compound that opens new possibilities for the treatment of pancreatic cancer. Inspired by the compound Nicolaioidesin C found in the medicinal plant Boesenbergia pandurata (Family: Zingiberaceae), the team discovered that the newly synthesized compound Nic-15, when combined with the chemotherapy drug gemcitabine, effectively delays or prevents the development of drug resistance and significantly reduces the size and growth of pancreatic cancer tumors.
Figure 1. Research outline
By specifically targeting the molecular pathways that allow cancer cells to survive, the Awale research team demonstrated that Nic-15 significantly enhances the efficacy of gemcitabine, leading to a substantial reduction in tumor growth in preclinical studies. This novel therapeutic approach offers a promising new avenue for combating pancreatic cancer, especially in cases where drug resistance has hindered treatment. This innovative research has been published in the Journal of Medicinal Chemistry and is attracting considerable attention.
Background of the Research
Pancreatic cancer is notorious for its low survival rate, with many patients being diagnosed at an advanced stage. Pancreatic cancer tumors are characterized by a hostile microenvironment with limited blood supply and nutrients. This unique environment allows cancer cells to evolve unique survival strategies. Traditional chemotherapy drugs often prove ineffective against these tumors, as they target rapidly dividing cells in nutrient-rich environments.
The research group led by Associate Professor Suresh Awale has developed a highly effective treatment strategy by targeting the specific mechanisms that allow cancer cells to survive in nutrient-deprived conditions. Nic-15, which specifically targets the pancreatic cancer microenvironment, shows the potential to treat cancer more effectively while minimizing damage to healthy cells.
Figure 2. Boesenbergia pandurata
Key Findings
- Innovative Treatment: Nic-15, a derivative of the plant-based compound Nicolaioidesin C, enhances the effectiveness of gemcitabine in treating pancreatic cancer.
- Overcoming Chemotherapy Resistance: The combination of Nic-15 and gemcitabine inhibits the survival pathways of cancer cells, reducing chemotherapy resistance.
- Significant Results: Preclinical studies have demonstrated the efficacy of this combination therapy in suppressing tumor growth.
Glossary
- Boesenbergia pandurata: Boesenbergia pandurata (Family: Zingiberaceae) is a perennial plant native to Southeast Asia. It has been used traditionally in Vietnam, Thailand, Indonesia, and other countries.
- Nicolaioidesin C: A compound found in Boesenbergia pandurata that has gained attention for its structure and biological activity, particularly its anti-tumor effects. It is a rare compound in the plant, making chemical synthesis crucial for detailed research.
- Nic-15: A new anti-cancer compound developed through organic synthesis, inspired by the structure of Nicolaioidesin C. It exhibits strong cytotoxicity against cancer cells, especially those in nutrient-poor conditions.
- Pancreatic Cancer Microenvironment: The tumor microenvironment in pancreatic cancer is characterized by poor blood supply and nutrient deficiency, allowing cancer cells to survive through a phenomenon known as “austerity,” which also increases malignancy and resistance to treatments like gemcitabine.
Details of the Paper
Title
Targeting Pancreatic Cancer with Novel Nicolaioidesin C Derivatives: Molecular Mechanism, In Vitro, and In Vivo Evaluations
Authors
Takeyoshi Yamazaki, Nguyen Duy Phan, Juthamart Maneenet, Mitsuki Yamagishi, Yuya Nishikawa, Takuya Okada, Tomoyuki Okumura, Naoki Toyooka, Tsutomu Fujii, and Suresh Awale*
Published In: Journal of Medicinal Chemistry
2024 Aug 22;67(16):14313-14328.