# Quantifying NNK metabolites to facilitate Kava lung cancer prevention clinical translation

> **NIH NIH R03** · UNIVERSITY OF FLORIDA · 2023 · $76,250

## Abstract

ABSTRACT
Lung cancer causes the most deaths among all cancers. Given the limited success in its early diagnosis and
clinical treatment, risk reduction is essential in order to improve lung cancer management. Tobacco cessation
should be the primary approach among smokers for lung cancer risk reduction. Current cessation interventions,
however, are not very effective. Preventing tobacco-induced carcinogenesis could be complementary.
Supported by human epidemiological data, pre-clinical animal data, a pilot trial, and equipped with mechanistic
insights, kava is a promising candidate to reduce lung cancer risk among addicted smokers. Kava, which
originates from the South Pacific Islands as a beverage, reduces stress and improves sleep. An inverse
relationship between kava consumption and cancer incidence, particularly lung cancer, among the South Pacific
Islanders suggests its potential in reducing cancer risks. We demonstrated that kava completely blocked lung
tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (a tobacco specific lung carcinogen,
commonly known as NNK) and other cancers in lab animals. One underlying mechanism is to enhance
carcinogen detoxification and thus reduce carcinogen-induced DNA damage. Consistent with lab animal data,
our pilot trial results showed that kava reduced lung cancer risk biomarkers among smokers. In order to improve
kava’s translational feasibility and to maximize its lung cancer preventive benefits, this self-contained study aims
to evaluate the potential of five mechanism-based non-invasive quantitative biomarkers in timely monitoring the
efficacy of kava intervention and more importantly to explore the opportunities of kava precision prevention
among smokers by analyzing these biomarkers and potential SNPs using banked pre-, during-, and post-kava
urine, plasma and buffy coat samples from 21 smoker participants. Aim 1. To quantify three NNK-based urinary
metabolites – free NNAL, NNAL-N-gluc and NNAL-O-gluc in the urine samples among 21 participants collected
from the pilot trial before kava exposure (Day 0), during kava exposure (Day 4), and after kava exposure (Day
7). Specific UGT SNPs will be analyzed as well. Aim 2. To quantify two NNK-based plasma protein adducts –
HPB and Diol in the plasma samples among 21 participants collected from the pilot trial before kava exposure
(Day 0), during kava exposure (Day 4), and after kava exposure (Day 7).

## Key facts

- **NIH application ID:** 10683294
- **Project number:** 5R03CA273467-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** CHENGGUO XING
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $76,250
- **Award type:** 5
- **Project period:** 2022-08-04 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683294

## Citation

> US National Institutes of Health, RePORTER application 10683294, Quantifying NNK metabolites to facilitate Kava lung cancer prevention clinical translation (5R03CA273467-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10683294. Licensed CC0.

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