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Targeting SRC to mediate solasonine's anti-cancer activity in hepatocellular carcinoma and its potential for
Zheng Liu1, Xiao Yang Xia2, Jia Yao Yang2
1Department of Integrated Traditional Chinese and Western Medicine, School of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, China.
Introduction:
Cancer remains a leading cause of mortality worldwide, with persistent therapeutic gaps across its heterogeneous subtypes. Solasonine, a steroidal glycoalkaloid from Solanum species, exhibits broad anti-tumor activity, yet its pan-cancer mechanisms of action remain poorly defined.
Methods:
A multi-tiered framework was employed: bibliometric analysis mapped the global research landscape; network pharmacology identified core solasonine-cancer target intersections, followed by GO and KEGG pathway enrichment and drug-target-pathway network construction; qRT-PCR, Western blotting, and CCK-8 assays in HCC cell lines experimentally validated the in silico-predicted hub target, SRC, and interrogated downstream signaling.
Results:
Bibliometric analysis showed solasonine research concentrated primarily on breast cancer, bladder cancer, and HCC. Network pharmacology identified eight core targets-SRC, EGFR, AKT1, CDH1, TNF, BCL2, ESR1, and STAT3-with SRC as the central network hub. Experimental validation confirmed solasonine suppressed SRC at both transcriptional and translational levels, and SRC overexpression significantly rescued solasonine-induced proliferative inhibition in HCC cells.
Discussion:
These integrated findings identify SRC as a critical mechanistic node mediating the pan-cancer anti-tumor effects of solasonine, particularly in HCC, and provide a rational foundation for its further development as a multi-target therapeutic agent.
Insights
Solasonine, a natural compound, shows anti-cancer effects by targeting the SRC protein. This research clarifies its mechanism, paving the way for new cancer therapies.
Area of Science:
- Pharmacology
- Oncology
- Bioinformatics
Background:
- Cancer is a major global health challenge with limited treatment options.
- Solasonine, a steroidal glycoalkaloid, has demonstrated anti-tumor properties, but its mechanisms are not fully understood.
- Understanding solasonine's action is crucial for developing novel cancer therapeutics.
Purpose of the Study:
- To elucidate the pan-cancer mechanisms of action of solasonine.
- To identify key molecular targets and pathways affected by solasonine.
- To validate the role of a specific target, SRC, in solasonine's anti-cancer activity.
Main Methods:
- Bibliometric analysis to map global research trends.
- Network pharmacology to identify solasonine-cancer target intersections.
- Gene Ontology (GO) and KEGG pathway enrichment analysis.
- Experimental validation using qRT-PCR, Western blotting, and CCK-8 assays in HCC cell lines.
Main Results:
- Bibliometric analysis highlighted research focus on breast cancer, bladder cancer, and hepatocellular carcinoma (HCC).
- Network pharmacology identified SRC as the central hub among eight core targets (SRC, EGFR, AKT1, CDH1, TNF, BCL2, ESR1, STAT3).
- Experimental validation confirmed solasonine suppresses SRC expression and activity, and SRC inhibition mediates solasonine's anti-proliferative effects in HCC.
Conclusions:
- SRC is identified as a critical mechanistic node for solasonine's pan-cancer anti-tumor effects.
- These findings support solasonine's potential as a multi-target therapeutic agent for cancer, especially HCC.
- Further development of solasonine is warranted based on its validated anti-cancer mechanisms.
