ArticleJournal of experimental & clinical cancer research : CR2015
Inactivation of PI3-K/Akt and reduction of SP1 and p65 expression increase the effect of solamargine on suppressing EP4 expression in human lung cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 42 citations in OpenAlex.
- Genome-wide analyses of long noncoding RNA expression profiles in lung adenocarcinoma.Scientific reports · 2017Trial
- Unveiling the Dual Mechanisms ofInternational journal of molecular sciences · 2026Article
- Solamargine inhibited the progression of non-small cell lung cancerEuropean journal of histochemistry : EJH · 2025Article
- Mettl1-mediated mInternational journal of biological sciences · 2025Article
- Literature-based Survey of Medicinal Plants Since 1900: A Case Study to Treat Cancer in the Sultanate of Oman.Current topics in medicinal chemistry · 2025Review
- Article
- Main chemical constituents and mechanism of anti-tumor action of Solanum nigrum L.Cancer medicine · 2024Review
- An Update on Potential Molecular Biomarkers of Dietary Phytochemicals Targeting Lung Cancer Interception and Prevention.Pharmaceutical research · 2023Review
- Active components of Solanum nigrum and their antitumor effects: a literature review.Frontiers in oncology · 2023Review
- α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer.Open life sciences · 2023Article
- Solamargine induces hepatocellular carcinoma cell apoptosis and autophagy via inhibiting LIF/miR-192-5p/CYR61/Akt signaling pathways and eliciting immunostimulatory tumor microenvironment.Journal of hematology & oncology · 2022Article
- Hidden in Plants-A Review of the Anticancer Potential of the Solanaceae Family in In Vitro and In Vivo Studies.Cancers · 2022Review
- Anticancer activity of glycoalkaloids fromFrontiers in pharmacology · 2022Review
- Solamargine Alleviates Proliferation and Metastasis of Cervical Cancer Cells by Blocking the CXCL3-Mediated Erk Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Identification of solamargine as a cisplatin sensitizer through phenotypical screening in cisplatin-resistant NSCLC organoids.Frontiers in pharmacology · 2022Article
- Solamargine Alleviated UVB-Induced Inflammation and Melanogenesis in Human Keratinocytes and MelanocytesFrontiers in medicine · 2022Article
- MicroRNA-499 serves as a sensitizer for lung cancer cells to radiotherapy by inhibition of CK2α-mediated phosphorylation of p65.Molecular therapy oncolytics · 2021Article
- Qing-Kai-Ling Injection Acts Better Than Shen-Fu Injection in Enhancing the Antitumor Effect of Gefitinib in Resistant Non-Small Cell Lung Cancer Models.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Integrin αVβ5/Akt/Sp1 pathway participates in matrix stiffness-mediated effects on VEGFR2 upregulation in vascular endothelial cells.American journal of cancer research · 2020Article
- The regulation and interaction of colon cancer-associated transcript-1 and miR7-5p contribute to the inhibition of SP1 expression by solamargine in human nasopharyngeal carcinoma cells.Phytotherapy research : PTR · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung cancer is the most common cause of cancer-related deaths worldwide. Natural phytochemicals from traditional medicinal plants such as solamargine have been shown to have anticancer properties. The prostaglandin E2 receptor EP4 is highly expressed in human cancer, however, the functional role of EP4 in the occurrence and progression of non small cell lung cancer (NSCLC) remained to be elucidated.
methodsCell viability was measured by MTT assays. Western blot was performed to measure the phosphorylation and protein expression of PI3-K downstream effector Akt, transcription factors SP1, p65, and EP4. Quantitative real-time PCR (qRT-PCR) was used to examine the mRNA levels of EP4 gene. Exogenous expression of SP1, p65, and EP4 genes was carried out by transient transfection assays. EP4 promoter activity was measured by Dual Luciferase Reporter Kit.
resultsWe showed that solamargine inhibited the growth of lung cancer cells. Mechanistically, we found that solamargine decreased the phosphorylation of Akt, the protein, mRNA expression, and promoter activity of EP4. Moreover, solamargine inhibited protein expression of SP1 and NF-κB subunit p65, all of which were abrogated in cells transfected with exogenous expressed Akt. Intriguingly, exogenous expressed SP1 overcame the effect of solamargine on inhibition of p65 protein expression, and EP4 protein expression and promoter activity. Finally, exogenous expressed EP4 feedback reversed the effect of solamargine on phosphorylation of Akt and cell growth inhibition.
conclusionOur results show that solamargine inhibits the growth of human lung cancer cells through inactivation of Akt signaling, followed by reduction of SP1 and p65 protein expression. This results in the inhibition of EP4 gene expression. The cross-talk between SP1 and p65, and the positive feedback regulatory loop of PI3-K/Akt signaling by EP4 contribute to the overall responses of solamargine in this process. This study unveils a novel mechanism by which solamargine inhibits growth of human lung cancer cells.
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