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Zerumbone induces apoptosis in human renal cell carcinoma via Gli-1/Bcl-2 pathway
Yi Sun1, Qiu Sheng, Yongyi Cheng
1Department of Urology, Shaanxi Provincal People's Hospital, Xi'an, P. R. China. adoremidfall@yahoo.cn
Abstract:
Renal cell carcinoma (RCC) is a malignant disease insensitive to conventional treatments such as radiochemotherapy and immunotherapy. Search for new approaches to induce cancer cell apoptosis will improve the management of RCC. Here, we reported that zerumbone, a monosesquiterpine, shows anticancer effects on human RCC cells via induction of apoptosis in vitro. Human renal clear cell carcinoma 786-0 and 769-P cell lines were used as the model system. Exposure of RCC cells to zerumbone resulted in cell viability inhibition, accompanied by DNA fragmentation and increased apoptotic index. Mechanically, treatment of RCC cells with zerumbone activated caspase-3 and caspase-9, and finally led to cleavage of PARR In addition, downregulation of Gli-1 and Bcl-2, which were closely related to the chemoresistance of RCC, was observed in zerumbone-treated RCC cells. Taken together, our study provided the first evidence that zerumbone imparted strong inhibitory and apoptotic effects on human RCC cells. The zerumbone-induced apoptosis might be related to the activation of the caspase cascade and deregulation of the Gli-1/Bcl-2 pathway. Our results suggest that zerumbone merit further investigation as an apoptosis inducer as well as a novel RCC chemotherapeutic agent in the clinical setting.
Insights
Zerumbone, a natural compound, effectively inhibits renal cell carcinoma (RCC) growth by inducing cancer cell apoptosis. This study highlights zerumbone
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Renal cell carcinoma (RCC) exhibits resistance to conventional therapies like radiochemotherapy and immunotherapy.
- Novel therapeutic strategies targeting cancer cell apoptosis are crucial for improving RCC management.
Purpose of the Study:
- To investigate the anticancer effects of zerumbone, a monoterpene, on human renal cell carcinoma (RCC) cells.
- To elucidate the molecular mechanisms underlying zerumbone-induced apoptosis in RCC cells.
Main Methods:
- Human RCC cell lines (786-0 and 769-P) were treated with zerumbone.
- Cell viability, DNA fragmentation, and apoptotic index were assessed.
- Caspase activation, PARP cleavage, and expression levels of Gli-1 and Bcl-2 were analyzed.
Main Results:
- Zerumbone significantly inhibited RCC cell viability and induced DNA fragmentation.
- Treatment with zerumbone activated caspase-3 and caspase-9, leading to PARP cleavage.
- Zerumbone downregulated the expression of Gli-1 and Bcl-2, proteins associated with RCC chemoresistance.
Conclusions:
- Zerumbone demonstrates potent inhibitory and apoptosis-inducing effects on human RCC cells.
- The mechanism involves activation of the caspase cascade and deregulation of the Gli-1/Bcl-2 pathway.
- Zerumbone warrants further investigation as a potential novel chemotherapeutic agent for RCC.
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