Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea

• DOI: 10.1007/s00280-011-1591-2
• Publication Date: 2011-03-12T02:24:08Z
• Authors: Bret Bannerman; Ling Xu; Matthew Jones; Christopher Tsu; Jie Yu; Paul Hales; Johan Monbaliu; Paul Fleming; Lawrence Dick; Mark Manfredi; Christopher Claib...; Joseph Bolen; Erik Kupperman; Allison Berger
• Keywords: Gallate; Component (thermodynamics)

To investigate whether clinically relevant levels of epigallocatechin gallate (EGCG, a component green tea) or vitamin C (ascorbic acid) could antagonize bortezomib antitumor activity in CWR22 human prostate xenograft tumors.The pharmacokinetics (PK) EGCG and ascorbic acid were determined immunocompromised mice compared with concentrations measured PK studies dietary supplements. Antitumor combination was using several dosing regimens to evaluate different target plasma acid.Bortezomib dosed twice-weekly at 0.8 mg/kg IV demonstrated tumor growth inhibition (TGI) 53.9-58.9%. However, when combined such that the >200 μM time dosing, all abrogated (TGI = -17.7%). A lower concentration (11-16 μM), which is severalfold higher than humans taking supplements (0.6-3 not antagonistic 63.5%). Pharmacodynamic proteasome reflected these findings. Ascorbic (40 500 PO daily) evaluated under similar study design did 57.2 72.2%).No antagonism seen preclinical vivo experiments, where are commensurate supplemental intake. The data suggest patients receiving treatment do need avoid normal consumption tea, C-containing foods,