| Title: |
2'-Hydroxyflavanone inhibits proliferation, tumor vascularization and promotes normal differentiation in VHL-mutant Renal Cell Carcinoma |
| Authors: |
Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Lelsani, Poorna; Prokai, Laszlo; Awasthi, Sanjay; Singhal, Sharad S. |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2011 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Cancer Prevention |
| Description: |
Renal cell carcinoma (RCC) is one of the top ten cancers prevalent in USA. Loss-of-function mutations in the VHL gene constitute an established risk factor contributing to 75% of total reported cases of RCC. Loss of VHL leads to a highly vascularized phenotype of renal tumors. Intake of citrus fruits has been proven to reduce the risk of RCC in multi-center international studies. Hence, we studied the effect of 2 ' -hydroxyflavanone (2HF), an active anti-cancer compound from oranges, in RCC. Our in vitro investigations revealed that 2HF suppresses VHL -mutant RCC to a significantly greater extent than VHL -wild type RCC by inhibiting EGFR signaling which is increased due to VHL mutations in RCC. Our results also revealed for the first time, that 2HF inhibits GSTπ activity. 2HF reduced cyclin B1 and CDK4 levels and induced G2/M phase arrest in VHL -mutant RCC. Importantly, 2HF inhibited the angiogenesis in VHL -mutant RCC by decreasing VEGF expression. Our in vivo studies in mice xenografts confirmed our in vitro results as evident by decreased levels of proliferation marker, Ki67 and angiogenic marker, CD31, in 2HF treated mice xenografts of VHL -mutant RCC. 2HF also increased the expression of E-cadherin in VHL -mutant RCC which would be of significance in restoring normal epithelial phenotype. Collectively, our in vitro and in vivo results revealed the potent anti-proliferative, anti-angiogenic and pro-differentiation properties of 2HF in VHL -mutant RCC, sparing normal cells, which could have significant implications not only in the specific management of VHL -mutant RCC but also towards other VHL syndromes. |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://carcin.oxfordjournals.org/cgi/content/short/bgr021v1; http://dx.doi.org/10.1093/carcin/bgr021 |
| DOI: |
10.1093/carcin/bgr021 |
| Availability: |
http://carcin.oxfordjournals.org/cgi/content/short/bgr021v1; https://doi.org/10.1093/carcin/bgr021 |
| Rights: |
Copyright (C) 2011, Oxford University Press |
| Accession Number: |
edsbas.E7D0E6DC |
| Database: |
BASE |