New role of lupeol in reticence of angiogenesis, the cellular parameter of neoplastic progression in tumorigenesis models through altered gene expression.

Abstract

There is a major unmet medical need for effective and well tolerated treatment options for cancer. The search now seeks to identify active biomolecules with multiple targets. Lupeol, an important dietary triterpenoid known as anticarcinogen by inducing apoptosis. But it is still more to reveal the potency of lupeol in the inhibition of neovascularization in cancer context. The study aimed to explore the efficacy of the lupeol in targeting angiogenesis. In this study, the inhibition of neovessel formation was assessed by preliminary antiangiogenesis assays like chorio allontoic membrane (CAM) and rat corneal micro pocket models. Further, validated for the micro vessel density (MVD) in histological sections of peritoneum, solid tumor and xenograft tumor by immunostaining with anti CD31 antibody. Antitumor potency was verified in ascites carcinoma, solid lymphoma and human nueroblastoma xenograft in CAM. Altered angiogenic gene expression by RT-PCR, ELISA and gelatin zymography. Lupeol significantly inhibits the neovessel formation in CAM and in the rat cornea. The similar effect was ascertained in mice and human xenograft tumor models with the regressed growth. Eventually reflecting on the differential transcription of angiogenic genes like MMP-2 & 9, HIF-1α, VEGFa and Flt-1 was noteworthy. It is now evident from our studies that, a new avenue of dietary triterpenoid lupeol by targeting angiogenesis, potentially inferring the multimode action in cancer prevention.

• Authors: B R Vijay Avin, T Prabhu, C K Ramesh, V Vigneshwaran, Mahmood Riaz, K Jayashree, B T Prabhakar
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 448 Issue 2 Pg. 139-44 (May 30 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24780400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Pentacyclic Triterpenes
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• lupeol

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Chick Embryo
• Chorioallantoic Membrane (blood supply, drug effects, pathology)
• Cornea (blood supply, drug effects)
• Gene Expression Regulation (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Lymphoma (drug therapy, pathology)
• Male
• Matrix Metalloproteinase 2 (genetics)
• Matrix Metalloproteinase 9 (genetics)
• Mice
• Neovascularization, Pathologic (drug therapy, genetics)
• Pentacyclic Triterpenes (pharmacology)
• Rats
• Vascular Endothelial Growth Factor A (genetics)
• Xenograft Model Antitumor Assays