ORIGINAL RESEARCH article
Front. Oncol.
Sec. Genitourinary Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1633891
Ginsenoside Rh2 repressed the progression of prostate cancer through the mitochondrial damage induced by mitophagy and ferroptosis
Provisionally accepted
- 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- 2The Second Hospital of Tianjin Medical University, Tianjin, China
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Prostate cancer (PC) is the most common malignancy of the male genitourinary system and the second leading cause of cancer deaths in men globally. Many patients develop resistance, progressing to castrationresistant prostate cancer (CRPC), a more aggressive and treatmentinsensitive form of the disease. Therefore, developing more effective treatments for PC is critical. Ginsenoside Rh2 (GRh2), a bioactive compound derived from ginseng, demonstrates promising antitumor potential in tumors. This study demonstrates that GRh2 potently inhibits proliferation, migration, and invasion of PC3 cells (IC50 = 19.3 μg/ml).Mechanistically, GRh2 induces mitochondrial dysfunction (depolarized membrane potential, elevated ROS, disrupted ATP/ADP) and activates mitophagy, evidenced by enhanced PINK1/Parkin expression, reduced mitochondrial proteins (VDAC1/TOM20), and autophagosome formation.Concurrently, GRh2 triggers ferroptosis, characterized by lipid ROS accumulation, increased MDA and Fe²⁺, GSH depletion, and downregulation of SLC7A11/GPX4. Critically, the effects on both pathways are reversible by specific inhibitors (Mdivi-1 for mitochondrial dysfunction/mitophagy, Fer-1 for ferroptosis), confirming their causal role in GRh2's action. Importantly, this study provides the first evidence that GRh2 orchestrates synergistic antitumor effects in prostate cancer through the mitochondrial damage induced by mitophagy and ferroptosis. In vivo, GRh2 effectively inhibits subcutaneous tumor growth in nude mice. These findings establish GRh2 as a multifaceted therapeutic agent against PC, operating through synergistic mitochondrial disruption pathways.
Keywords: Ginsenoside Rh2, PC, Mitochondrial damage, mitophagy, ferroptosis, Chinese medicine
Received: 23 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 He, Shi, Zhu, Tian, Zhang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhihong Zhang, The Second Hospital of Tianjin Medical University, Tianjin, China
Changwen Zhang, The Second Hospital of Tianjin Medical University, Tianjin, China
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