# Targeting phenethyl isothiocyanate to mitochondria in lung carcinogenesis

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2024 · $645,107

## Abstract

Project Summary
Disruption of normal mitochondrial bioenergetics and oxidative phosphorylation represents an early event during
oncogenesis by changing the energy metabolism of precancerous and cancerous cells. Phenethyl isothiocyanate
(PEITC), a natural compound present in cruciferous vegetables, has been shown to inhibit the development of
several types of cancer in animal models. PEITC has been shown to inhibit oxidative phosphorylation and to
induce cancer cell apoptosis through a mitochondria-dependent mechanism and ROS formation, suggesting the
role of mitochondrial bioenergetic function and redox homeostasis in oncogenesis. This provides the rationale
for conjugating PEITC to a targeting agent that drives it into mitochondria to specifically study the role of
mitochondrial function and ROS formation in lung cancer development and to increase the efficacy of PEITC.
Preliminary studies demonstrate that mitochondria-targeted PEITC (Mito-PEITC) is a significantly more potent
inhibitor of lung carcinogenesis in mice. We hypothesize that lung oncogenesis and metastasis depend on
mitochondrial respiration and that Mito-PEITC is a novel, potent inhibitor of lung carcinogenesis and metastasis
acting primarily through mitochondrial mechanisms. This hypothesis will be tested using three specific aims. Aim
1 will evaluate the preventive potential and mechanisms of action of Mito-PEITC in vitro. We will use Mito-PEITC
and lung cancer cells with genetically modified expression of the members of the mitochondrial electron transport
chain to decipher the oncogenic mechanism and evaluate the mechanisms of action of Mito-PEITC. Aim 2 will
determine preventive efficacy of Mito-PEITC on lung tumor initiation and progression in A/J mice. Aim 3 will
determine the in vivo mechanism and the efficacy of Mito-PEITC to inhibit lung cancer brain metastasis. We will
use state-of-the-art in vitro and in vivo assays, including small animal imaging technology to monitor the growth
of primary tumors (magnetic resonance imaging) and engraftment of metastatic cells. Innovative approaches for
in vivo monitoring of changes in cancer cell bioenergetics and cellular oxidant production (bioluminescence
imaging) will be employed. Defining mitochondrial mechanisms of lung oncogenesis and brain metastasis and
developing a novel, well-tolerated efficacious agent for prevention and treatment of lung cancer will be highly
significant.

## Key facts

- **NIH application ID:** 10811869
- **Project number:** 1R01CA280746-01A1
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** MING YOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,107
- **Award type:** 1
- **Project period:** 2024-02-02 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811869

## Citation

> US National Institutes of Health, RePORTER application 10811869, Targeting phenethyl isothiocyanate to mitochondria in lung carcinogenesis (1R01CA280746-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10811869. Licensed CC0.

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