Ginsenoside Rh4 Triggers Ferroptosis in Lung Cancer: Targeting KEAP1/NRF2/HO-1 and Remodeling Gut Microbiota for Butyrate-Mediated ATF3 Activation
Qihan Zhu, Wenxuan Xu, Ge Yang, Yansong Gao, Yujuan Zhao, Zijian Zhao, You Kang, Shengyu Li, Lei Zhao
TL;DR
Ginsenoside Rh4 fights lung cancer by triggering cell death through iron overload and gut microbiota changes that boost butyrate and ATF3 activity.
Contribution
This study reveals a novel anti-cancer mechanism of ginsenoside Rh4 via ferroptosis and gut microbiota remodeling.
Findings
Ginsenoside Rh4 induces ferroptosis in lung cancer cells by disrupting iron homeostasis and antioxidant defenses.
In vivo, ginsenoside Rh4 suppresses tumor growth and alters gut microbiota to increase butyrate and ATF3 activity.
The KEAP1/NRF2/HO-1 pathway is inhibited, enhancing ferroptosis sensitivity through GPX4 suppression.
Abstract
Lung cancer progression is regulated by multiple factors, including ferroptosis and gut microbiota-mediated butyrate metabolism. This study investigates the anti-tumor effects of ginsenoside Rh4 on lung cancer cells via ferroptosis mechanisms in vitro and in vivo. In vitro, ginsenoside Rh4 inhibited the proliferation of Lewis lung carcinoma (LLC) and A549 cells and triggered ferroptosis, effects that were suppressed by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). In vivo, tumor-bearing mouse models were established and treated with 100 mg/kg ginsenoside Rh4 for 21 days. Tumor growth, ferroptosis markers, gut microbiota, and butyrate were analyzed, with in vitro validation of butyrate’s pathway effects. Ginsenoside Rh4 induced ferroptosis in LLC cells both in vitro and in vivo, inhibiting tumor growth. It promoted ferroptosis by disrupting iron homeostasis through elevated Fe2+ and…
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Taxonomy
TopicsFerroptosis and cancer prognosis · Immune cells in cancer · Gut microbiota and health