# Oral Epigallocatechin Gallate (EGCG) for Treatment of Cisplatin Ototoxicity

> **NIH NIH R01** · SOUTHERN ILLINOIS UNIVERSITY SCH OF MED · 2022 · $356,488

## Abstract

Cisplatin is a widely used chemotherapeutic agent for the treatment of a variety of human cancers. However, the
therapeutic benefits of this drug are compromised by dose limiting side effects such as ototoxicity, nephrotoxicity
and neurotoxicity. The incidence of cisplatin-induced hearing deficits, assessed by audiometric studies, range
from 75-100%. In the pediatric population, where cisplatin is used to treat neuroblastomas and central nervous
system malignancies, loss of hearing could hamper speech, cognition and social development of the child. Other
drugs, such as carboplatin and oxaliplatin, have emerged as alternatives to cisplatin, but their usefulness is
limited to a few cancers and they produce consistent neuropathies. Cisplatin is shown to be more effective than
carboplatin in treating non-small-cell lung cancer even though the side effects of the two drugs appear equivalent.
Thus, cisplatin still retains its importance as a component of the chemotherapeutic regimen for various cancers.
While the mechanism of chemotherapeutic efficacy of cisplatin appears to be DNA alkylation, the generation of
reactive oxygen species (ROS) via NOX3 NADPH oxidase appears critical for mediating cisplatin ototoxicity and
nephrotoxicity. This has stimulated interest for using antioxidants as otoprotectants. A limitation of this approach,
however, is that thiol-containing antioxidants could interfere with cisplatin antitumor efficacy. We have recently
shown that signal transducer and activator of transcription 1 (STAT1) couples ROS (from cisplatin) to the
inflammatory cascade, which exacerbates hearing loss. We also shown that knockdown of STAT1 (by siRNAs)
protects against cisplatin-induced hearing loss. Moreover, our preliminary data show that epigallocatechin gallate
(EGCG), the most abundant catechin in green tea and an inhibitor of STAT1 protects against cisplatin ototoxicity.
Interestingly, EGCG also activates STAT3, a transcription factor linked to cell survival. These dual mechanisms
of otoprotection by EGCG would be explored in more detail in this grant proposal. An added advantage of EGCG
is that it possesses intrinsic anticancer properties and does not interfere with cisplatin chemotherapeutic efficacy
in initial studies. The goals of this proposal are to determine the efficacy of oral EGCG against cisplatin
ototoxicity and nephrotoxicity in rats (Specific aims 1). The mechanisms underlying the protective action
of EGCG against cisplatin ototoxicity, focusing on the STAT1 and STAT3 pathways and gene expression
analysis, will be examined in Specific aim 2. Specific aim 3 will determine potential antitumor interference
by EGCG against different tumor cells in xenograft mouse models. The results provided in this study would
provide a better understanding of the utility of EGCG for the treatment of cisplatin oto- and nephrotoxicity and
could support its therapeutic use in cancer patients. Furthermore, this study should expand our knowledge
concernin...

## Key facts

- **NIH application ID:** 10405612
- **Project number:** 5R01DC016835-05
- **Recipient organization:** SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
- **Principal Investigator:** LEONARD P RYBAK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $356,488
- **Award type:** 5
- **Project period:** 2018-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405612

## Citation

> US National Institutes of Health, RePORTER application 10405612, Oral Epigallocatechin Gallate (EGCG) for Treatment of Cisplatin Ototoxicity (5R01DC016835-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10405612. Licensed CC0.

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