Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors

Encouse B. Golden, Philip Y. Lam, Adel Kardosh, Kevin J. Gaffney, Enrique Cadenas, Stan G. Louie, Nicos A. Petasis, Thomas C. Chen, Axel H. Schönthal

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this "miracle herb" in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (BZM) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid-based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.

Original languageEnglish (US)
Pages (from-to)5927-5937
Number of pages11
JournalBlood
Volume113
Issue number23
DOIs
StatePublished - Nov 17 2009
Externally publishedYes

Fingerprint

Boronic Acids
Proteasome Inhibitors
Polyphenols
Tea
Cell death
Multiple Myeloma
Tumors
Neoplasms
Cell Death
Nelfinavir
Caspase 7
Endoplasmic Reticulum Stress
Chemotherapy
Proteasome Endopeptidase Complex
Glioblastoma
Bortezomib
Chemical activation
Cells
Drug Therapy
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Golden, E. B., Lam, P. Y., Kardosh, A., Gaffney, K. J., Cadenas, E., Louie, S. G., ... Schönthal, A. H. (2009). Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood, 113(23), 5927-5937. https://doi.org/10.1182/blood-2008-07-171389

Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. / Golden, Encouse B.; Lam, Philip Y.; Kardosh, Adel; Gaffney, Kevin J.; Cadenas, Enrique; Louie, Stan G.; Petasis, Nicos A.; Chen, Thomas C.; Schönthal, Axel H.

In: Blood, Vol. 113, No. 23, 17.11.2009, p. 5927-5937.

Research output: Contribution to journalArticle

Golden, EB, Lam, PY, Kardosh, A, Gaffney, KJ, Cadenas, E, Louie, SG, Petasis, NA, Chen, TC & Schönthal, AH 2009, 'Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors', Blood, vol. 113, no. 23, pp. 5927-5937. https://doi.org/10.1182/blood-2008-07-171389
Golden, Encouse B. ; Lam, Philip Y. ; Kardosh, Adel ; Gaffney, Kevin J. ; Cadenas, Enrique ; Louie, Stan G. ; Petasis, Nicos A. ; Chen, Thomas C. ; Schönthal, Axel H. / Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. In: Blood. 2009 ; Vol. 113, No. 23. pp. 5927-5937.
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