# SESN2 and therapeutic effect of Isohapontigenin (ISO)

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $422,055

## Abstract

Project Summary
Human bladder cancer is the sixth most common cancer in the United States. Discovery and evaluation of new
alternative medications is of tremendous importance for reducing the bladder cancer mortality. Chinese herb
Gnetum Cleistostachyun has been used for treatment of bladder cancers for centuries, but its bioactive
components and anti-cancer mechanisms have been barely explored. Our recent studies discovered that
Isorhapontigenin (ISO), a new derivative of stilbene compound isolated from this herb, exhibited multiple anti-
cancer activities in human high grade invasive bladder cancer cells. Our preliminary studies provided strong
evidence on ISO inhibition of tumor growth both in vitro and in vivo. In addition, the robust induction of SESN2
and BECN1, the important autophagy regulator and effector, have been shown as a critical event for ISO's
anti-cancer activity in vitro, as depletion of either SESN2 or BECN1 significantly impaired the capacity of ISO to
inhibit tumor cell growth. However, many questions, such as whether ISO affects cell invasion and tumor
metastasis in vivo, and whether SESN2/BECN1 mediates ISO's in vivo activity, as well as upstream regulators
being responsible for their upregulation by ISO, remain unknown. Therefore, in this application, three specific
aims were proposed to address key events in SESN2/BECN1-mediated ISO tumor inhibition. The first Aim will
target the potential upstream regulators and epigenetic mechanism that mediate ISO-induced upregulation of
SESN2 and BECN1. The second Aim will employ both in vitro and in vivo approaches to address the functional
relevance of SESN2 and BECN1 as well as new candidates obtained from Aim 1 in ISO inhibition of tumor
invasion and metastasis. The last Aim will focus on in vivo role of SESN2 and BECN1 in BC development
using BBN-induced mouse bladder carcinogenic model. The results obtained from the proposed studies will
determine whether ISO specifically initiates the SESN2/BECN1/autophagy pathway to inhibit bladder tumor
formation, invasion, and metastasis. The success of this proposal will facilitate our understanding of the
molecular basis of ISO anti-cancer activity and will also provide new insights for developing a better
therapeutic strategy for human high grade invasive bladder cancer.

## Key facts

- **NIH application ID:** 9849751
- **Project number:** 5R01CA217923-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Max Costa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,055
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849751

## Citation

> US National Institutes of Health, RePORTER application 9849751, SESN2 and therapeutic effect of Isohapontigenin (ISO) (5R01CA217923-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849751. Licensed CC0.

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