Monday, June 30, 2025 6/30/2025

Oral Epigallocatechin Gallate (EGCG) for Treatment of Cisplatin Ototoxicity

Award Number: R01DC016835
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Oral Epigallocatechin Gallate (EGCG) for Treatment of Cisplatin Ototoxicity - 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 concerning the importance of STAT1/STAT3 balance in hair cell survival.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE	801 N RUTLEGE	SPRINGFIELD	IL	62794	SANGAMON	USA	Research Related to Deafness and Communication Disorders	000	5	3/5/2024	NON-COMPETING CONTINUATION	$0
2024	2022	SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE	801 N RUTLEGE	SPRINGFIELD	IL	62794	SANGAMON	USA	Research Related to Deafness and Communication Disorders	001	5	4/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $356,488 )
2022	2022	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Research Related to Deafness and Communication Disorders	000	5	5/18/2022	NON-COMPETING CONTINUATION	$356,488
														Subtotal = $356,488

Issue Date FY: 2021 ( Subtotal = $728,931 )
2021	2021	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Research Related to Deafness and Communication Disorders	001	4	5/14/2021	NON-COMPETING CONTINUATION	$367,187
2021	2021	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Research Related to Deafness and Communication Disorders	000	3	4/8/2021	SUPPLEMENT FOR EXPANSION	$361,744
														Subtotal = $728,931

Issue Date FY: 2020 ( Subtotal = $361,208 )
2020	2020	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Research Related to Deafness and Communication Disorders	000	3	5/12/2020	NON-COMPETING CONTINUATION	$361,208
														Subtotal = $361,208

Issue Date FY: 2019 ( Subtotal = $392,079 )
2019	2019	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Research Related to Deafness and Communication Disorders	000	2	5/16/2019	NON-COMPETING CONTINUATION	$392,079
														Subtotal = $392,079

Issue Date FY: 2018 ( Subtotal = $403,954 )
2018	2018	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Research Related to Deafness and Communication Disorders	000	1	5/29/2018	NEW	$403,954
														Subtotal = $403,954

Grand Total All Awards = $2,242,660

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Oral Epigallocatechin Gallate (EGCG) for Treatment of Cisplatin Ototoxicity

Award Number: R01DC016835

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer