# Chemoprevention Efficacy of Sulforaphane Against Obesity-Induced Endometrial Carcinogenesis

> **NIH NIH P30** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $145,000

## Abstract

The obesity epidemic has contributed to increased incidence and mortality of endometrial cancer (EC) in the
United States, particularly among younger women. Although EC is associated with a good prognosis in
comparison to other cancers, surgery remains the cornerstone therapy for EC patients due to loss of hormone
receptors contributing hormonal resistance in more than 30% cases. However, surgery is not a good option for
obesity-related co-morbid conditions, and women of childbearing age, which prevents individual’s candidacy for
surgical operation. Therefore, newer prevention strategies are needed to reduce EC incidence, morbidity,
mortality, and to save fertility. In the search for new preventive drugs for EC, we demonstrated significant anticancerous activity of sulforaphane (SFN), a naturally occurring dietary isothiocyanate, in-vivo and in-vitro, in
addition to its Histone deacetylase (HDAC) inhibition activity in EC. Due to the lack of significant toxicity in normal
cells, SFN has garnered significant attention as a cancer preventive agent for humans: currently, several ongoing
phase-I and phase-II clinical trials are evaluating its chemo-preventive role in different types of cancers.
Furthermore, recent studies have established SFN’s critical role in the management of obesity and obesityrelated disorders. SFN has been shown to regulate adipogenesis and lipogenesis, as well as apoptosis and
lipolysis in adipocytes. Since regulation of the key risk factor, obesity, as well as regression or treatment of EC
precursor lesions such as endometrial hyperplasia (AEH/EH) to normal endometrium are rational approaches to
prevent EC development, we hypothesized that SFN is a promising chemo-preventive agent for EC due to its
ability to regulate obesity and exert anti-proliferative activity on the endometrium. We also expect that the HDAC
inhibition activity of SFN will contribute to enhanced sensitivity of progesterone therapy via upregulation of the
progesterone receptors. Therefore, in this study, we propose to develop an obesity-associated animal model of
AEH/EH to explore the underlying mechanism and association of obesity with the development of AEH/EH. We
also plan to evaluate the chemo-preventive efficacy of SFN alone or in combination with progesterone besides
exploring the anti-obesity mechanism of SFN in our obesity associated EH/AEH animal model. This project fits
within the parent grant goal to raise the standard of care and improve clinical outcomes for all women with
gynecologic cancers with an emphasis on addressing cancer problems relevant to Oklahoma. Oklahoma has
highest rates of obesity and worst records of the US States for nutrition and women’s health care. The
mechanistic insight into how obesity drives EC, gained from this study will be used to develop novel molecularly
targeted intervention strategies. Establishing SFN as a therapeutic alternative for AEH may provide a less
invasive and less costly preventive strategy for EC. Fu...

## Key facts

- **NIH application ID:** 10285647
- **Project number:** 3P30CA225520-04S1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** ROBERT S. MANNEL
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $145,000
- **Award type:** 3
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285647

## Citation

> US National Institutes of Health, RePORTER application 10285647, Chemoprevention Efficacy of Sulforaphane Against Obesity-Induced Endometrial Carcinogenesis (3P30CA225520-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10285647. Licensed CC0.

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