ArticleBMC complementary medicine and therapies2024
Shikonin reactivates TSGs GADD45B and PPP3CC to block NSCLC cell proliferation and migration through JNK/P38/MAPK signaling pathways.
Article in BMC complementary medicine and therapies, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 7 citations in OpenAlex.
- GADD45B promotes apoptosis in intestinal ischemia/reperfusion through DNA demethylation of MST1/Hippo.Chinese medical journal · 2026Article
- TLCD1 correlates with malignant progression of hepatocellular carcinoma and activation of the ERK signaling cascade.Scientific reports · 2026Article
- Effects of Lycium barbarum Polysaccharide on Digestive Function and Intestinal Barrier Dysfunction in Septic Mice by Regulating JNK Pathway.Molecular biotechnology · 2025Article
- Calcineurin in cancer signaling networks.Nagoya journal of medical science · 2025Review
- Enhancing recovery in non-small cell lung cancer patients through mindfulness training and Jinshui Liujun decoction supplementation.World journal of psychiatry · 2025Article
- Systematic bioinformatics analysis identifies shikonin as a novel mTOR pathway inhibitor in triple-negative breast cancer progression.Frontiers in pharmacology · 2025Article
- Mindfulness-based stress reduction training and supplemented Jinshui Liujun decoction promote recovery in patients with non-small cell lung cancer.World journal of psychiatry · 2024Article
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6 authors at 3 institutions in 1 country.
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Abstract
backgroundShikonin, a natural naphthoquinone compound extracted from the Chinese traditional herbal medicine "Lithospermum erythrorhizon", possesses antitumor activity against various cancer types. Tumor-suppressor genes (TSGs) negatively regulate cell growth, proliferation, and differentiation, thereby inhibiting tumor formation. However, the molecular mechanism of action of shikonin on TSGs in non-small-cell lung cancer (NSCLC) remains unclear.
methodsThe inhibitory effect of shikonin on the proliferation and migration abilities of lung cancer cells were measured by Cell Counting Kit 8 (CCK8) and wound healing assays. The alteration of genes by shikonin treatment was detected by mRNA high-throughput sequencing and further confirmed by qPCR and western blotting experiments. The dominant functions of the upregulated genes were analyzed by GO and KEGG profiling.
resultsShikonin inhibited the proliferation and migration of A549 and H1299 NSCLC cells in a dose-dependent manner. mRNA high-throughput sequencing revealed a total of 1794 upregulated genes in shikonin-treated NSCLC cells. Moreover, bioinformatic analysis of GO and KEGG profiling revealed that the up-regulated genes were mostly involved in the JNK/P38/MAPK signaling pathway, among which the expression of GADD45B and PPP3CC was significantly enhanced. Finally, we confirmed that GADD45B and PPP3CC were indeed upregulated in JNK/P38/MAPK pathway.
conclusionsTaken together, these results suggested that shikonin might affect the expression of GADD45B and PPP3CC through the JNK/P38/MAPK pathway, therefore exerting an inhibitory effect on the proliferation and migration of cancer cells. To our knowledge, this is the first study reporting the role of shikonin in upregulating TSGs to activate the JNK/P38/MAPK signaling pathways in NSCLC.
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