In vitro cytotoxicity of (-)-EGCG octaacetate on MDAMB-231 and SKHep-1 human carcinoma cells: A pharmacological consideration on prodrug design

Stanton Hon Lung Kok, Raymond Siu Ming Wong, Roberto Gambari, Filly Cheung, Wing Sze Lam, Fung Yi Lau, Gregory Yin Ming Cheng, Chor Hing Cheng, Kim Hung Lam, Sau HIng Chan, Cheuk On Tang, Chung Hin Chui, Kwok Ping Ho

Research output: Journal article publicationJournal articleAcademic researchpeer-review

6 Citations (Scopus)


Esterification of acetate with generic pharmaceutical compound has been commonly employed to produce ester prodrug for improving its potency when compared with the mother compound. Acetate, on the other hand, has been recognized to have inhibitory effect on the respiratory biochemistry. Here we demonstrate that acetate at a concentration of 400 μM exhibited significant growth inhibitory activity on two human cancer cell lines, the MDAMB-231 breast cancer and the SKHep-1 hepatoma cell lines. To establish the ester prodrug with multi-acetate ester conjugates as our experimental model, one molecule of (-)-epigallocatechin gallate was required to conjugate with eight molecules of acetate forming the corresponding (-)-epigallocatechin gallate octaacetate prodrug. Chemical structure of this epigallocatechin gallate octaacetate ester prodrug was confirmed by both 13C and 1H nuclear magnetic resonance spectra and mass spectrometry. Further cytotoxic assay using both MDAMB-231 and SKHep-1 human carcinoma cell lines showed that acetate at a concentration of 400 μM exhibits an additional cytotoxic effect with (-)-epigallocatechin gallate at a concentration of 50 μM, although the additional effect was not as high as (-)-epigallocatechin gallate octaacetate ester prodrug alone at a concentration of 50 μM. Our results thus raise a pharmacological consideration of using multi-acetate conjugate as the ester prodrug where the release of free acetate by esterase could be part of the explanation for the improved in vitro cytotoxicity.
Original languageEnglish
Pages (from-to)841-845
Number of pages5
JournalInternational Journal of Molecular Medicine
Issue number6
Publication statusPublished - 1 Dec 2008


  • (-)-EGCG
  • (-)-EGCG octaacetate prodrug
  • Acetate

ASJC Scopus subject areas

  • Genetics

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