# Mechanistic Insight on the Role of Berberine and AMPK in Hepatocellular Carcinoma

> **NIH NIH R03** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $79,950

## Abstract

Project Summary
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide including
the United States due to late detection and limited effective therapeutic options. Sorafenib is the
only FDA-approved drug currently available with limited efficacy for a small window of time.
Designing effective therapeutic strategies to combat HCC is a major long-term focus of the
current proposal. This proposal is based on our recent observations that revealed: (i) treatment
of various HCC cells with the natural compound Berberine (BBR) reduces cell viability, (ii) BBR
increases apoptosis in combination with proapoptotic TRAIL, (iii) TRAIL-BBR combination-
induced apoptosis requires active AMP-activated protein Kinase (AMPK) signaling, (iv) BBR
activates AMPK, (v) BBR antagonizes β-catenin expression and inhibits β-catenin/TCF-
mediated downstream signaling. Based on these we hypothesize that BBR-induced AMPK
activation represents a novel therapeutic strategy for treating HCC, which via inhibiting β-
catenin/TCF axis can antagonize HCC progression. In this pilot proposal, using biochemical, cell
biological and in vivo approaches we plan on generating strong supporting data to validate our
hypothesis so more elaborate studies with BBR can be designed in the future. Two specific
aims are proposed: (Aim 1) Elucidate the role of AMPK in mediating BBR-induced antagonism
of HCC and its potential crosstalk with β-catenin and (Aim 2) Determine the efficacy of BBR and
AMPK in antagonizing HCC progression in a mouse model of HCC. While Aim 1 studies are
expected to provide a mechanistic insight towards the signaling pathway by which BBR
antagonizes HCC and reveal a potential crosstalk between AMPK and Wnt/β-catenin axes,
those in Aim 2 will provide important preclinical information on the in vivo efficacy of BBR-
mediated AMPK activation on HCC. Successful outcome of the studies proposed will provide
newer insights towards developing BBR-based mono or combination therapeutic strategies in
the future for the targeting of HCC.

## Key facts

- **NIH application ID:** 9850549
- **Project number:** 5R03CA219764-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** BASABI RANA
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,950
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850549

## Citation

> US National Institutes of Health, RePORTER application 9850549, Mechanistic Insight on the Role of Berberine and AMPK in Hepatocellular Carcinoma (5R03CA219764-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9850549. Licensed CC0.

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