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Inhibition of cancer stem cell self-renewal by a platinum(II) complex suppresses metastasis in gastrointestinal cancer

ABSTRACT: Cancer stem cells (CSCs) drive therapy resistance, metastasis, and relapses in gastrointestinal cancers, highlighting the need for novel strategies to target this subpopulation. Here, we characterize the platinum(II) complex trans-[PtI₂(isopropylamine)₂] (I5) as a potent inhibitor of CSC-associated pathways and functions in gastric and pancreatic cancer models. Transcriptomic and functional analyses reveal that I5 markedly suppresses Hedgehog, NOTCH, and JAK/STAT signaling, leading to reduced expression of pluripotency markers (NANOG, SOX2, OCT3/4), CSC surface antigens (CD133, CXCR4), and diminished tumorosphere formation. I5 also induces mitochondrial dysfunction, oxidative stress, and metabolic impairment in CSC-enriched populations. In vivo, I5 pre-treatment significantly impairs tumor initiation and metastatic potential in xenograft models. Unlike cisplatin, I5 overcomes platinum resistance by targeting core self-renewal and survival mechanisms in CSCs. These findings position I5 as a promising therapeutic.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296719 | GEO | 2025/12/16

REPOSITORIES: GEO

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