β-Ionone represses renal cell carcinoma progression through activating LKB1/AMPK-triggered autophagy
Tao Hou1,2,3, Yuzhao Wang1,2,3, Weichao Dan1,2,3
1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Abstract:
β-Ionone, the end ring analog of β-carotenoids, has been proven to have an antitumor effect in a variety of cancers. In this study, we investigated the impact of β-ionone on renal cell carcinoma (RCC) cell lines (786-O and ACHN) using colony formation assays, flow cytometry analysis, and western blot analysis. We found that β-ionone effectively inhibited the proliferation of RCC cells in vitro, which was also confirmed in a xenograft model. Moreover, we found that β-ionone could induce autophagy, as indicated by LC3 puncta in 786-O and ACHN cell lines and the expression of LC3 in β-ionone-treated RCC cells. To further explore the underlying mechanism, we assessed liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) signaling pathway activity, and the results showed that β-ionone inhibited the proliferation of RCC cells by inducing autophagy via the LKB1/AMPK signaling pathway. In summary, our findings provide a new therapeutic strategy of β-ionone-induced autophagy in RCC.
Insights
Beta-ionone effectively inhibits renal cell carcinoma (RCC) proliferation by inducing autophagy. This study reveals a new therapeutic strategy for RCC through beta-ionone-induced autophagy via the LKB1/AMPK pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Beta-ionone, a beta-carotenoid analog, exhibits antitumor properties across various cancer types.
- Renal cell carcinoma (RCC) remains a significant challenge in cancer treatment.
- Understanding novel therapeutic agents for RCC is crucial.
Purpose of the Study:
- To investigate the effects of beta-ionone on renal cell carcinoma (RCC) cell lines.
- To elucidate the mechanism by which beta-ionone impacts RCC proliferation and survival.
- To explore the potential of beta-ionone as a therapeutic strategy for RCC.
Main Methods:
- In vitro studies using RCC cell lines (786-O and ACHN) with colony formation assays, flow cytometry, and western blot analysis.
- In vivo validation using a xenograft mouse model.
- Assessment of autophagy markers (LC3 puncta and expression) and the LKB1/AMPK signaling pathway.
Main Results:
- Beta-ionone significantly inhibited RCC cell proliferation in vitro and in vivo.
- Beta-ionone treatment induced autophagy in RCC cells, evidenced by increased LC3 puncta and expression.
- The antiproliferative effect of beta-ionone was mediated by autophagy induction through the LKB1/AMPK signaling pathway.
Conclusions:
- Beta-ionone demonstrates potent antitumor activity against renal cell carcinoma.
- Beta-ionone-induced autophagy, via the LKB1/AMPK pathway, represents a novel therapeutic mechanism for RCC.
- Beta-ionone holds promise as a potential therapeutic agent for treating renal cell carcinoma.
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