Gedunin abrogates aldose reductase, PI3K/Akt/mToR, and NF-κB signaling pathways to inhibit angiogenesis in a hamster model of oral carcinogenesis

• DOI: 10.1007/s13277-015-4003-0
• Publication Date: 2015-09-05T20:41:14Z
• Authors: Kranthi Kiran Kis...; Raghu Ganugula; Deepak Reddy Gade; Geereddy Bhanupra...; Siddavaram Nagini
• Keywords: IκB kinase

Aberrant activation of oncogenic signaling pathways plays a central role in tumor development and progression. The aim this present study was to investigate the chemopreventive effects neem limonoid gedunin hamster model oral cancer based on its ability modulate aldose reductase (AR), phosphatidyl inositol-3-kinase (PI3K)/Akt, nuclear factor kappa B (NF-κB) block angiogenesis. Administration suppressed HBP carcinomas by inhibiting PI3K/Akt NF-κB through inactivation Akt inhibitory kinase (IKK), respectively. Immunoblot molecular docking interactions revealed that inhibition these may be mediated via AR gedunin. Gedunin blocked angiogenesis downregulating expression miR-21 pro-angiogenic factors vascular endothelial growth hypoxia inducible factor-1 alpha (HIF-1α). In conclusion, results provide compelling evidence prevents progression buccal pouch (HBP) kinases Akt, IKK, AR, transcription HIF-1α