New role of lupeol in reticence of angiogenesis, the cellular parameter of neoplastic progression in tumorigenesis models through altered gene expression.
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.
Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577203, Karnataka, India.
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Vijay Avin
Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577203, Karnataka, India.
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Prabhu
Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577203, Karnataka, India.
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Ramesh
Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577203, Karnataka, India.
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Vigneshwaran
Postgraduate Department of Studies and Research in Biotechnology, Jnana Sahyadri Campus, Kuvempu University, Shimoga 577203, Karnataka, India.
Mahmood
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Riaz
Department of Pathology, JSS Medical College, JSS University, Mysore 570015, Karnataka, India.
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Jayashree
Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga 577203, Karnataka, India. Electronic address: pbtssc@gmail.com.
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Prabhakar
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000094042:Lupanes
D020533:Angiogenesis Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053978:Pentacyclic Triterpenes; D042461:Vascular Endothelial Growth Factor A; C497442:HIF1A protein, human; C467484:VEGFA protein, human; C010480:lupeol; D000094042:Lupanes
Antiangiogenesis; Lupeol; Neovascularization; VEGF