Abstract
Nobiletin, a flavonoid found chiefly in oranges and lemons, has exhibited potential anti-proliferative and pro-apoptotic activities in various types of cancers. However, the inhibitory effect and mechanisms of nobiletin on renal cancer cells are unclear. CCK8 and plate clone formation assay were used to determine the effect of nobiletin on the proliferation of renal cancer cells, while scratch healing test was used to assay its effect on migration ability. The effect of nobiletin on the invasion of renal cancer cells was determined using Trans well chamber assay. Flow cytometry was used to determine the effect of nobiletin on apoptosis of renal cancer cells, while Western blotting assay was used to determine its effect on the expressions of JAK2/STAT3 and PI3K/Akt pathway proteins, and apoptosis-related proteins. Nobiletin inhibited the proliferation of renal carcinoma cells in a time- and dose-dependent manner. It inhibited the migration and invasion of renal cancer cells, and promoted their apoptosis. Western blot results showed that nobiletin inhibited the phosphorylations of JAK2, STAT3, PI3K, and Akt, and promoted the expressions of apoptosis-related proteins. Nobiletin inhibits the proliferation, invasion and migration of renal cell carcinoma by inhibiting JAK2/STAT3 and PI3K/Akt pathways, and promotes their apoptosis. These findings provide a new experimental basis for the application of nobiletin in the treatment of renal cancer.
Highlights
Renal cell carcinoma (RCC), the most common types of renal carcinoma, occurs mainly in renal tubular epithelial cells, and accounts for more than 90% of all renal tumors [1,2]
Flow cytometry was used to determine the effect of nobiletin on apoptosis of renal cancer cells, while Western blotting assay was used to determine its effect on the expressions of JAK2/STAT3 and PI3K/Akt pathway proteins, and apoptosis-related proteins
In order to elucidate the potential mechanism involved in the anti-renal cancer effect of nobiletin, this study investigated the effect of nobiletin on the proliferation of renal cancer cells, and its effect on the JAK2/STAT3 and PI3K/Akt signaling pathways
Summary
Renal cell carcinoma (RCC), the most common types of renal carcinoma, occurs mainly in renal tubular epithelial cells, and accounts for more than 90% of all renal tumors [1,2]. The most common among these is clear cell carcinoma which accounts for about 60 to 85% of RCC. The pathogenesis of clear cell carcinoma is from Von Hippel-Lindau (VHL) gene mutations which lead to increased activity of hypoxia inducible factor 1 (HIF 1) and angiogenesis. The high cost of targeted drug therapyandsurgical trauma has become a huge challenge for patients. Another approach is to consume anticancer foods, with the aim of preventing kidney cancer. Flavonoids, found mainly in vegetables and citrus fruits, have anti-inflammatory, anti-angiogenic and pro-apoptotic effects [4,5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
