The anticancer action of plant polyphenols in Hodgkin’s lymphoma cells

G. G. MACKENZIE; N. QUEISSER; M. L. WOLFSON; N.P. DECKER; C. G. FRAGA; A. M. ADAMO; P. I. OTEIZA

Jaipur, India

Congreso; Society for Free Radical Research-India, VII Annual Meeting; 2008

Although treatment of Hodgkin’s lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease.  Thus, the current goal in HL treatment is to find therapies that specifically target constitutively deregulated signaling cascades, such as NF-kB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. We are investigating the capacity of several polyphenols, i.e. (-)-epicatechin (EC), dimeric procyanidin B2 (B2), and curcumin to inhibit NF-kB and STAT3, and prevent H-RS cell proliferation and induce apoptosis. In H-RS cells, EC and B2 inhibited NF-kB but did not affect STAT3 activation, causing a moderate decrease in H-RS cell viability (15-40%).  EC and B2 specifically acts inhibiting NF-êB by preventing the binding of the active NF-êB to the DNA. Curcumin inhibited both, NF-kB and STAT3 activation, leading to a decreased expression of proteins involved in cell proliferation and apoptosis. Curcumin induced cell cycle arrest in G2-M and apoptotic cell death, causing a significant reduction (80-97%) in H-RS cell viability. The present results stress the concept that several signaling pathways should be considered when designing new therapies for HL, and that select polyphenols can be of relevant value in the targeted treatment of HL.