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Cardamomin Inhibits the Proliferation and Tumorigenesis of Bladder Cancer by ESR1 in PI3K/AKT Pathway
Peng Zhang1, Dapeng Song2, Zhidong Fang3
1Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Insights
Cardamomin demonstrates significant anti-cancer effects on bladder cancer by inhibiting cell proliferation and invasion. This natural compound upregulates ESR1 expression and impacts the PI3K/AKT pathway, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cardamomin, a compound from cardamom, has shown anti-cancer properties in various studies.
- Its specific role and mechanism in bladder cancer, particularly concerning the PI3K/AKT pathway, remain underexplored.
Purpose of the Study:
- To investigate the anti-cancer effects of cardamomin on bladder cancer cells.
- To elucidate the underlying molecular mechanisms, focusing on the Estrogen Receptor 1 (ESR1) and the PI3K/AKT signaling pathway.
Main Methods:
- In vitro studies utilized CCK8 assays, proliferation, apoptosis, and cell migration analyses on bladder cancer cell lines (5637 and HT1376).
- Western blot and RT-qPCR were employed to assess ESR1 expression and PI3K/AKT pathway activity.
- In vivo experiments involved subcutaneous tumor models in mice, evaluating tumor growth, KI67 expression, apoptosis (TUNEL assay), and pathway markers.
Main Results:
- Cardamomin significantly inhibited bladder cancer cell proliferation, invasion, and G0/G1 to S phase transition, while increasing apoptosis.
- It upregulated ESR1 expression and downregulated the PI3K/AKT pathway in both in vitro and in vivo models.
- In vivo studies confirmed cardamomin's tumor-inhibitory effects, reducing KI67-positive cells and increasing TUNEL-positive cells.
Conclusions:
- Cardamomin exhibits a potent inhibitory effect on bladder cancer progression.
- The anti-tumor activity is mediated through the upregulation of ESR1, leading to the downregulation of the PI3K/AKT pathway.
- Cardamomin represents a promising therapeutic candidate for bladder cancer treatment.
Abstract:
Cardamomin has been widely studied in cancer, but its role in cancer bladder cancer has not been mentioned. In this study, we validated the anti-cancer effect of cardamom and whether its potential mechanism is related to the PI3K/AKT pathway. After treating with different doses of cardamomin, the cytotoxicity was studied by CCK8. Secondly, we analyzed the effect of cardamomin on the proliferation, apoptosis and cell movement. Next, we analyzed the regulation of ESR1 by western blot and its impact on the PI3K/AKT pathway. We also transfected ESR1 overexpression and silencing vectors, and verified the transfection efficiency through RT-qPCR. Further, the specific mechanism of the drug's inhibitory effect on bladder cancer was also determined. We constructed the subcutaneous tumor model in vivo. After cardamomin administration, we mainly analyzed the positive expression of KI67 in tumor tissues by immunohistochemistry, and the apoptotic cells in tumor tissues by TUNEL, and related proteins in PI3K/AKT pathway by western blot. In this paper, cardamomin inhibited cell proliferation and invasion ability, blocked the transition of G0/G1 phase to S phase, and increased apoptotic rate of 5637 and HT1376 cells, as well as raised ESR1 expression. Cardamomin exerted anti-tumor effect through PI3K/AKT pathway. In vivo animal experiments indicated the inhibitory effect of cardamomin on subcutaneous implanted tumor. Cardamomin inhibited the positive expression of KI67 and promoted the TUNEL-positive cells in tumor tissues. Consistent with in vitro assay, cardamomin increased the expression of ESR1 and downregulated the PI3K/AKT pathway. Cardamomin has a significant inhibitory effect on bladder cancer, and upregulate the expression of ESR1 in bladder cancer through PI3K/AKT.
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