Polyphenon E is the trademarked name (by Mitsui Norin Co., Ltd.) of the catechin epigallocatechin-3-gallate abundant in green/ Chinese tea. It is in multiple clinical trials for cancer and other diseases . Notably it has shown an effect in early stage chronic lymphocytic leukemia (CLL) and hormone receptor negative breast cancer with possible but unconfirmed mechanisms involving down-regulation of vascular endothelial growth factor. [2, 3].
It is known that polyphenon E reduces the proliferation of pancreatic cancer cell lines. In the pancreatic cancer cell line MIA PaCa-2 polyphenon E was shown to alter the metabolic profile of the cells in a manner similar to the LDHA inhibitor oxamate . This suggests that LDHA and cancer metabolism could be the target of polyphenon E in pancreatic cancer, however confirmatory studies are required that directly demonstrate this.
Polyphenon E represents a potential drug where clinical evidence of effect in many diseases has been found before the basic mechanism of action has been determined. Moving forward it will be very important to pinpoint the molecular targets of polyphenon E as these may be novel, provide new insight into disease biology, and ultimately provide a rationale for the development of even more potent drugs to modulate those targets.
You never know the year of the monkey might not be so unlucky!
- ‘Search of: Polyphenon – List Results – ClinicalTrials.gov’. Accessed 10 February 2016. https://www.clinicaltrials.gov/ct2/results?term=polyphenon&pg=1.
- Shanafelt, Tait D., Timothy G. Call, Clive S. Zent, Jose F. Leis, Betsy LaPlant, Deborah A. Bowen, Michelle Roos, et al. ‘Phase 2 Trial of Daily, Oral Polyphenon E in Patients with Asymptomatic, Rai Stage 0 to II Chronic Lymphocytic Leukemia: EGCG for CLL’. Cancer 119, no. 2 (15 January 2013): 363–70. doi:10.1002/cncr.27719.
- Crew, K. D., P. Brown, H. Greenlee, T. B. Bevers, B. Arun, C. Hudis, H. L. McArthur, et al. ‘Phase IB Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women with Hormone Receptor-Negative Breast Cancer’. Cancer Prevention Research 5, no. 9 (1 September 2012): 1144–54. doi:10.1158/1940-6207.CAPR-12-0117.
- Lu, Qing-Yi, Lifeng Zhang, Jennifer K. Yee, Vay-Liang W. Go, and Wai-Nang Lee. ‘Metabolic Consequences of LDHA Inhibition by Epigallocatechin Gallate and Oxamate in MIA PaCa-2 Pancreatic Cancer Cells’. Metabolomics : Official Journal of the Metabolomic Society 11, no. 1 (February 2015): 71–80. doi:10.1007/s11306-014-0672-8.