ArticleDie Naturwissenschaften2025
Curcumin protects extracellular matrix to maintain microenvironmental stability inhibiting colon cancer metastasis through HPSE/IL-6/STAT5 axis.
Article in Die Naturwissenschaften, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Dual-targeted protein-coated PLGA nanoparticles for pancreatic cancer therapy: a novel approach using esculetin and curcumin.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The Role of NOL3 in Colon Adenocarcinoma Metastasis and Its Association With DNA Methylation.Human mutation · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Our previous research demonstrated that curcumin suppresses mouse colorectal cancer (CRC) cell CT26 migration and invasion by inhibiting heparanase (HPSE) mRNA expression. To further elucidate the mechanism of curcumin in human CRC treatment, we hypothesized that HPSE plays a pivotal role in human CRC metastasis and that curcumin inhibits this process by downregulating HPSE expression through epigenetic regulation mediated by non-coding RNAs. For further research, human CRC cells were infected with lentivirus to establish overexpression of HPSE cell lines and corresponding negative control cell lines. In vitro and in vivo experiments showed that curcumin inhibited the proliferation, migration, and metastasis of CRC cancer by inhibiting HPSE expression. In the tumor microenvironment, HPSE played an important role in activating the IL-6/STAT5 axis signaling pathway by destructing the extracellular matrix and releasing large number of cytokines, while changing the tumor microenvironment and EMT process, thus promoting tumor metastasis. RNA-seq analysis combined with qRT-PCR results showed that curcumin's inhibition of HPSE expression involved the regulation of non-coding RNAs. Taken together, our results suggested that HPSE promotes CRC metastasis by activating the IL-6/STAT5 signaling axis, disrupting the ECM, releasing cytokines, and altering the tumor microenvironment to facilitate EMT. Curcumin significantly inhibits CRC cell proliferation, migration, and metastasis by downregulating HPSE expression via non-coding RNAs, which related to IL-6/STAT5 axis signal pathways. This research provides a comprehensive understanding of the molecular mechanisms underlying curcumin's anti-CRC effects, emphasizing the role of HPSE and non-coding RNAs in tumor metastasis. These findings pave the way for the development of novel therapeutic strategies targeting HPSE and its regulatory pathways in CRC.
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Registered trials
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