Lathyrol inhibits the proliferation of Renca cells by altering expression of TGF-β/Smad pathway components and subsequently affecting the cell cycle
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Updated: Jan 14, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
1Department of Education, Shandong Provincial Hospital, Jinan, China.
Background:
Renal cell carcinoma (RCC) is a prevalent type of malignant tumor with high morbidity and mortality. The TGF-β/Smad signaling pathway plays a significant role in the development and progression of RCC.
Methods:
This study explored the effects of lathyrol on the proliferation of Renca mouse RCC cells through the inhibition of the TGF-β/Smad signaling pathway and cell cycle arrest. Bioinformatics analysis, cell culture experiments, and animal experiments were conducted to determine the effects of lathyrol on the activity, mRNA expression, and protein expression of RCC cells and RCC xenograft tumors, as well as the expression of cell cycle and cell cycle regulatory proteins.
Results:
Lathyrol treatment was positively correlated with the inhibitory effect on cell proliferation. The IC values of 786-O cells and Renca cells were comparable. In vitro, lathyrol promoted both protein and mRNA expression of TGF-β1 while increasing Smad6 protein expression and Smad2, Smad3, and Smad4 mRNA expression; concurrently, it suppressed the protein expression of Smad2, Smad3, Smad4, and Smad9. In vivo, lathyrol suppressed the mRNA and protein expression of TGF-β1, TGF-βR1, Smad2, Smad3, Smad4, and Smad9 in RCC xenografts; promoted the protein expression of Smad6; and decreased the protein expression of cyclin D1, cyclin B1, cyclin A1, cyclin E1, CDK6, CDK4, and CDK1 while increasing the expression of P16, P21, and P27.
Conclusion:
Lathyrol can repress the expression of key proteins in the TGF-β/Smad signaling pathway, impede signal transduction, arrest the cell cycle progression of Renca cells, and subsequently inhibit the proliferation of RCC cells. Future studies are needed to further explore the mechanism of lathyrol in RCC treatment.
Insights
Lathyrol inhibits renal cell carcinoma (RCC) proliferation by targeting the TGF-β/Smad pathway and arresting the cell cycle. This study demonstrates lathyrol
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) is a significant cause of cancer morbidity and mortality.
- The transforming growth factor-beta (TGF-β)/Smad signaling pathway is implicated in RCC development and progression.
Purpose of the Study:
- To investigate the anti-proliferative effects of lathyrol on Renca mouse RCC cells.
- To elucidate the mechanism involving inhibition of the TGF-β/Smad pathway and cell cycle arrest.
Main Methods:
- Utilized bioinformatics analysis, in vitro cell culture, and in vivo animal experiments.
- Assessed the impact of lathyrol on RCC cell activity, gene and protein expression, and tumor growth.
- Examined the expression of key proteins in the TGF-β/Smad pathway and cell cycle regulators.
Main Results:
- Lathyrol demonstrated a dose-dependent inhibition of RCC cell proliferation.
- In vitro, lathyrol modulated TGF-β1, Smad6, and other Smad proteins; in vivo, it suppressed TGF-β1, TGF-βR1, and Smad proteins while upregulating Smad6.
- Lathyrol decreased expression of cyclins and CDKs, and increased expression of P16, P21, and P27, indicating cell cycle arrest.
Conclusions:
- Lathyrol represses key TGF-β/Smad pathway proteins, hinders signal transduction, and induces cell cycle arrest in RCC cells.
- Lathyrol effectively inhibits RCC cell proliferation, suggesting its potential as a therapeutic agent.
- Further research is warranted to fully explore lathyrol's mechanism in RCC treatment.
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