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SH003 as a Redox-Immune Modulating Phytomedicine: A Ferroptosis Induction, Exosomal Crosstalk, and Translational Oncology Perspective
by
, , , , , and
Moon Nyeo Park
1
,
Md. Maharub Hossain Fahim
1,
Han Na Kang
2,
Hanul Bae
1,
Amama Rani
1,3,
Fahrul Nurkolis
4,5
,
Trina E. Tallei
6,7
,
Seong-Gyu Ko
1,8,* and
Bonglee Kim
1,8,*
1
Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
2
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea
3
Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad 13100, Pakistan
4
Master of Basic Medical Science, Faculty of Medicine, University Airlangga, Surabaya 60115, Indonesia
5
Faculty of Science and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta 55281, Indonesia
6
Department of Biology, Faculty of Mathematics and Natural Sciences, University Sam Ratulangi, Manado 95115, Indonesia
7
Department of Biology, Faculty of Medicine, University Sam Ratulangi, Manado 95115, Indonesia
8
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 05253, Republic of Korea
*
Authors to whom correspondence should be addressed.
Cancers 2025, 17(21), 3519; https://doi.org/10.3390/cancers17213519 (registering DOI)
Submission received: 3 October 2025
/
Revised: 25 October 2025
/
Accepted: 29 October 2025
/
Published: 31 October 2025
(This article belongs to the Special Issue Feature Review for Cancer Therapy: 2nd Edition)
Simple Summary
Cancer cells frequently evade cell death by suppressing ferroptosis and remodeling the immune microenvironment. SH003, a GMP-standardized herbal formulation, has shown promising preclinical and early clinical evidence of safety and efficacy. This review highlights how SH003 regulates redox signaling, induces ferroptotic vulnerability, and enhances antitumor immunity through STAT3/PD-L1 inhibition and macrophage/T cell activation. These network-level effects suggest SH003 as a representative phytomedicine that bridges traditional herbal therapy with modern precision oncology.
Abstract
Redox dysregulation, ferroptosis evasion, and immune suppression are major barriers in cancer therapy. SH003, a multi-herbal formulation standardized under GMP conditions and evaluated in early-phase clinical studies (NCT03081819; KCT0004770), demonstrated a favorable safety profile supporting its translational potential. Preclinical studies reveal that SH003 disrupts mitochondrial homeostasis, triggers endoplasmic reticulum stress apoptosis, and sensitizes resistant tumors to ferroptosis via suppression of the SLC7A11–GPX4 axis and NRF2 destabilization. In parallel, SH003 remodels tumor immunity by attenuating STAT3-driven PD-L1 signaling, promoting macrophage repolarization, and enhancing cytotoxic lymphocyte activity. Exosome-associated microRNAs further suggest SH003’s role in redox–immune communication, although functional validation is pending. Collectively, SH003 represents a clinically tested phytomedicine that integrates ferroptosis induction with immune modulation, offering a biomarker-informed approach to precision oncology.
