Journal Article

2′-Hydroxyflavanone inhibits proliferation, tumor vascularization and promotes normal differentiation in <i>VHL</i>-mutant renal cell carcinoma

Lokesh Dalasanur Nagaprashantha, Rit Vatsyayan, Jyotsana Singhal, Poorna Lelsani, Laszlo Prokai, Sanjay Awasthi and Sharad S. Singhal

in Carcinogenesis

Volume 32, issue 4, pages 568-575
Published in print April 2011 | ISSN: 0143-3334
Published online February 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr021
2′-Hydroxyflavanone inhibits proliferation, tumor vascularization and promotes normal differentiation in VHL-mutant renal cell carcinoma

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Renal cell carcinoma (RCC) is one of the top ten cancers prevalent in USA. Loss-of-function mutations in the von Hippel–Lindau (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 multicenter international studies. Hence, we studied the effect of 2′-hydroxyflavanone (2HF), an active anticancer 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 epidermal growth factor receptor signaling, which is increased due to VHL mutations in RCC. Our results also revealed for the first time, that 2HF inhibits glutathione S-transferase pi 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 vascular endothelial growth factor 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 antiproliferative, anti-angiogenic and prodifferentiation 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.

Journal Article.  6504 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.