Epigallocatechin‐3‐gallate delivers hydrogen peroxide to induce death of ovarian cancer cells and enhances their cisplatin susceptibility

Abstract

The green tea polyphenol epigallocatechin-3-gallate (EGCG) has cancer chemopreventive properties against various types of cancers. The compound is known to attack various targets in transformed cells. In this report, we examined the action of EGCG on ovarian cancer cells. Eight ovarian cancer cell lines were tested (SKOV3, CAOV3, OVCAR3, OVCAR10, A2780, CP70, C30, and C200) and showed IC50s for EGCG at the micromolar range, including ones that are resistant to the chemotherapeutic drug cisplatin. The ovarian cancer cells were sensitive to H2O2 at similar concentrations, and EGCG treatment led to enhanced intracellular H2O2. Neutralization with pyruvate, a scavenger of H2O2, suggests that the toxicity of EGCG may be mediated by oxidative stress from the free radical. Addition of Tempol, a superoxide dismutase mimetic, demonstrates that H2O2 might be generated endogenously from superoxide. The toxicity of cisplatin and the development of cisplatin resistance are major obstacles in treatment of ovarian cancer. We found that addition of EGCG amplified the toxicity of cisplatin. EGCG increased cisplatin potency by three to six-fold in SKOV3, CAOV3, and C200 cells, the latter being a cell line induced to have several hundred fold resistant to cisplatin above the parental line. Our findings suggest that EGCG may accentuate oxidative stress to inhibit growth of ovarian cancer cells and sensitize them to cisplatin.

Epicatechin protects the auditory organ by attenuating cisplatin-induced ototoxicity through inhibition of ERK

“…EGCG increased cisplatin potency by three to six-fold in ovarian cancer cells. They suggest that EGCG may accentuate oxidative stress to inhibit growth of ovarian cancer cells and sensitize them to cisplatin (Chan et al, 2006). In our in vitro study, EC and other green tea extracts do not appear to interfere with the antitumor effect of chemotherapeutic agents (data not shown).…”

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy

“…5 Regarding EGCG-induced generation of ROS, hydrogen peroxide production induced by EGCG has been associated with 3-to 6-fold enhancement of cisplatin efficacy in ovarian cancer cells, even in some cell lines highly resistant to the treatment with the drug alone. 24 In leukemia cancer cells, co-treatment with arsenic trioxide (ATO) and EGCG showed oxidative-mediated induction of mitochondrial-dependent apoptosis. 25 EGCG increased intracellular hydrogen peroxide in cancer cells and ATO-induced heme oxygenase-1 (HO-1) provided ferrous iron thus increasing Fenton reaction and, as a consequence, oxidative damage to cells.…”

Epicatechin protects auditory cells against cisplatin-induced death

“…In addition, Chan et al found that EGCG amplified the toxicity of cisplatin: EGCG increased cisplatin potency by three to 6-fold in ovarian cancer cells [44]. They suggested that EGCG may accentuate oxidative stress to inhibit growth of ovarian cancer cells and sensitize them to cisplatin [45].…”