Biocatalytic Polymerization of Naturally Occurring Green Tea Flavonoids for Cancer TherapyEPA Grant Number: SU832474
Title: Biocatalytic Polymerization of Naturally Occurring Green Tea Flavonoids for Cancer Therapy
Investigators: Nagarajan, Subhalakshmi , Braunhut, Susan J. , Kumar, Jayant , Nagarajan, Ramaswamy
Current Investigators: Nagarajan, Subhalakshmi , Braunhut, Susan J. , Kumar, Jayant
Institution: University of Massachusetts - Lowell
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: September 30, 2005 through May 30, 2006
Project Amount: $10,000
RFA: P3 Awards: A National Student Design Competition for Sustainability Focusing on People, Prosperity and the Planet (2005) RFA Text | Recipients Lists
Research Category: Nanotechnology , P3 Challenge Area - Materials & Chemicals , Pollution Prevention/Sustainable Development , P3 Awards , Sustainability
The upsurge in the discovery, development and use of new materials and drugs has resulted in large-scale production of potentially toxic, carcinogenic intermediates and by-products leading to an outburst in the number of cancer cases. In the U.S. alone one in four deaths are caused by cancer. Ironically, most drugs that are used to treat cancer are synthesized using multiple steps that involve the use of carcinogenic chemicals (e.g., the use of pyridine in the synthesis of commercially available anticancer drug, Taxolâ). Although, natural compounds such as Epigallocatechin gallate (EGCG) have been known to exhibit inhibitory effects on the growth of cancer cells, they have limited stability and solubility in benign solvents. In recent years, polymeric drugs have been very successful as non-antibiotic remedies for the treatment of ailments.
We propose a novel strategy to polymerize, naturally occurring compounds such as catechins (obtained from green tea), using environmentally friendly methods (enzymes catalysis) to create poly(catechins) with promising anti-tumorigenic activity. Various stereoisomers of catechin [(+), (-), ( ")] will be biocatalytically polymerized using plant peroxidases in aqueous media and in the presence of biocompatible polyelectrolyte templates. This one-pot oxidative polymerization is carried out in ambient conditions yielding water-soluble poly(catechins). The starting materials, intermediates and the products obtained are completely biocompatible and therefore do not have any harmful effects to human life/environment. The polyelectrolyte template provides a unique local environment to promote the polymerization as well as impart solubility to the final poly(catechin). The non-toxic nature of the process and aqueous solubility of the poly(catechins) facilitates ease of deliverability of these materials into biological systems. Polymerization significantly enhances the efficiency of these materials in cancer therapy. Poly(catechins) have greater growth inhibitory effects and higher specificity towards highly metastatic cells as opposed to normal cells.
A new “green” method for the synthesis of water-soluble poly(catechins) will be developed and optimized. These poly(catechins) will be spectroscopically characterized and their inhibitory effects on the growth of breast and colon cancer cells as well as normal human epithelial cells will be systematically evaluated. Their activity will also be compared with monomeric catechins. A group of graduate and undergraduate students in UMass Lowell will be involved in developing and evaluating these anti-tumorigenic compounds using totally green synthetic protocol and in line with the P3 concepts. It is envisioned that the synthesis of anti-cancer drugs from bio-based materials, using green methods will cause a paradigm shift in the development of cancer drugs.