Polyphenon E, An Egcg Containing Green Tea Extract That Inhibits Tumor Growth, Has No Impact On Wound Collagen Content Or Clinical Rate of Wound Infection Or Dehiscence Yet Has a Mild Inhibitory Effect On Healing As Judged By Tensometry
Aviad Hoffman*1, Raymond Baxter1, Abu Nasar1, Thomas R. Gardner3, Kumara H. Shantha1, Keith Hoffman1, Richard L. Whelan1
1Surgery, Columbia University, New York, NY; 2Pathology, Columbia University, NY, NY; 3Orhtopedics, Columbia University, NY, NY
Introduction: Catechins in green tea, in particular EGCG (epigallocatechin-3-gallate), inhibit tumor growth in many murine models. Polyphenon E (PolyE) is a concentrated mixture of catechins (65% EGCG) with minimal side affects in humans that has stronger anti-cancer effects than tea alone. Surgery is associated with increased rates of tumor growth and metastases postoperatively(postop) in the murine setting. Perioperative (periop) administration of Poly E may limit surgery’s tumor stimulatory effects. Prior to a Phase 1 study, PolyE’s effects on wound healing must be studied. This study's purpose was to assess PolyE’s impact on laparotomy wound strength and collagen content.
Methods: Balb/C mice were randomized to plain water (Control, n=20) or a 1% PolyE solution (n=25) for drinking;10 days later all mice underwent sham laparotomy that was suture closed. Mice were sacrificed on postop days (PODs) 7 or 21 and the abdominal wall pelts were harvested. The peak force and total energy required to rupture each wound was determined via tensometry; wound collagen content was determined via a Sircol Collagen assay. Serum EGCG levels were determined in 3 PolyE mice on POD1, 7, and 21 to verify drug ingestion. Results are presented as mean ± SD; data was assessed using the student’s t-test and Mann-Whitney U-test (significance, p<0.05).
Results: No wound infections or dehiscences were noted in either group. The mean peak rupture force for each group was statistically similar on POD 7 and 21. There was no statistical difference in the total energy required for rupture on POD 7, however, on POD 21 the total energy required in the PolyE group (4.1 ± 0.78 N-mm) was significantly lower than for the control mice (5.6 ± 1.7 N-mm; p=0.026). When the 2 groups wound collagen results on POD 7 were compared there was no difference noted, the same was true for the POD 21 results. EGCG was detected in the PolyE mice serum on POD 1 and POD 7; on POD21 very low levels were detected.
Conclusions: Perioperative PolyE administration was not associated with wound complications. The peak force for rupture and the collagen content was similar at both time points for the 2 groups as was total energy for rupture on POD 7; total energy on POD 21 was less for the PolyE group. PolyE warrants further study as a perioperative anti-cancer agent in the cancer setting.
