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image of Network Pharmacology and Validation Experiments Reveal Cryptotanshinone Inhibits Acute Myeloid Leukemia Progression by Activating Endoplasmic Reticulum Stress

Abstract

Background

Acute myeloid leukemia (AML) is the most common adult hematologic malignancy, with relapse and drug resistance posing major challenges despite treatment advances. Cryptotanshinone (CTS), a diterpenoid compound derived from , exhibits anticancer activity in various tumors. However, its role and mechanisms in AML remain unclear. This study aims to investigate the inhibitory effects of CTS on AML cells and its potential mechanisms.

Methods

Network pharmacology was employed to identify potential AML-related targets of CTS, and a disease-drug-target interaction network was constructed. The effects of CTS on KG-1 cells were assessed using CCK-8 proliferation assays, cell cycle analysis and apoptosis detection. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to analyze the regulatory effects of CTS on the endoplasmic reticulum stress (ERS) signaling pathway. The role of the Hippo-YAP signaling pathway in CTS-induced AML inhibition was further explored.

Results

Network pharmacology analysis identified key AML-related targets of CTS, enriched in multiple cancer-related signaling pathways. Experimental results showed that CTS inhibited KG-1 cell proliferation in a dose-dependent manner, induced S-phase arrest, and promoted apoptosis. Furthermore, CTS treatment significantly upregulated ERS-related key proteins. While YAP overexpression attenuated CTS-induced ERS activation and reduced apoptosis levels.

Conclusion

This study indicates that CTS inhibits AML cell proliferation and induces apoptosis while activating the ERS signaling pathway. However, aberrant activation of the Hippo-YAP pathway weakens this effect. These findings provide novel theoretical insights into potential therapeutic strategies for AML.

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2025-07-01
2025-09-08

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Network Pharmacology and Validation Experiments Reveal Cryptotanshinone Inhibits Acute Myeloid Leukemia Progression by Activating Endoplasmic Reticulum Stress
Bentham Science Publishers ; https://doi.org/10.2174/0109298673348269250611042934
/content/journals/cmc/10.2174/0109298673348269250611042934
/content/journals/cmc/10.2174/0109298673348269250611042934
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  • Article Type:     Research Article
Keywords: endoplasmic reticulum stress ; Western blot ; network pharmacology ; natural compounds ; acute myeloid leukemia ; Cryptotanshinone

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