# Ponicidin Inhibits Lung Cancer Progression Through Coordinated Downregulation of Sulfhydryl Antioxidants and TrxR1

## TL;DR

Ponicidin, a natural compound, inhibits lung cancer growth by disrupting antioxidant systems and causing oxidative stress, with minimal harm to normal cells.

## Contribution

The study reveals ponicidin's novel antitumor mechanism in lung cancer through sulfhydryl antioxidant depletion and TrxR1 downregulation.

## Key findings

- Ponicidin significantly inhibits lung cancer cell viability with minimal toxicity to normal lung cells.
- Ponicidin induces oxidative stress, ER stress, mitochondrial dysfunction, and DNA damage in lung cancer cells.
- In vivo, ponicidin reduces tumor growth in mice without significant toxicity.

## Abstract

Ponicidin, a bioactive diterpenoid derived from Rabdosia rubescens, has been shown to exhibit antitumor activity across a range of cancer types. Despite its potential therapeutic applications, the precise effects and underlying molecular mechanisms of ponicidin in the context of lung cancer remain insufficiently characterized. This study aims to investigate the antitumor effects of ponicidin in lung cancer, focusing on its impact on cell growth and cellular oxidative stress. Our findings demonstrate that ponicidin significantly inhibits the viability of lung cancer cells while exhibiting minimal cytotoxicity to normal lung cells. Notably, ponicidin induces cell death in lung cancer cells via the induction of oxidative stress, a process likely mediated by the depletion of sulfhydryl antioxidants and the downregulation of thioredoxin reductase (TrxR), both of which play critical roles in maintaining cellular redox homeostasis. Moreover, ponicidin was found to concurrently activate endoplasmic reticulum stress, induce mitochondrial dysfunction, and promote DNA damage, further contributing to its antitumor effects. In vivo, the efficacy of ponicidin was confirmed in tumor-bearing mouse models, where ponicidin treatment led to a significant reduction in tumor growth without significant toxicity or adverse effects on the animals. These findings suggest that ponicidin holds significant promise as a safe and effective therapeutic agent for lung cancer, warranting further investigation into its clinical applicability.