Nimbolide upregulates RECK by targeting miR-21 and HIF-1α in cell lines and in a hamster oral carcinogenesis model

Scientific Reports
Jaganathan KowshikS Nagini

Abstract

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a potent inhibitor of matrix metalloproteinases (MMPs) is a common negative target of oncogenic signals and a potential therapeutic target for novel drug development. Here, we show that sequential RECKlessness stimulates angiogenesis and Notch signalling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model, a paradigm for oral oncogenesis and chemointervention. We also report the chemotherapeutic effect of nimbolide, a limonoid from the neem tree (Azadirachta indica) based on the upregulation of RECK as well as modulation of the expression of key molecules involved in invasion and angiogenesis. We demonstrate that nimbolide upregulates RECK by targeting miR-21, and HIF-1α resulting in reduced MMP activity and blockade of VEGF and Notch signalling. Nimbolide reduced microvascular density, confirming its anti-angiogenic potential. Molecular docking analysis revealed interaction of nimbolide with HIF-1α. Additionally, we demonstrate that nimbolide upregulates RECK expression via downregulation of HIF-1α and miR-21 by overexpression and knockdown experiments in SCC4 and EAhy926 cell lines. Taken together, these finding...Continue Reading

References

Aug 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Taku TakeuchiYoshiyuki Nakajima
Mar 1, 2012·PloS One·Dharmalingam SubramaniamPrateek Sharma
Jun 15, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Subash C GuptaBharat B Aggarwal
Aug 15, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kun-Hung ShenPin-Shern Chen
Dec 18, 2014·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·X Q ZhouH W Wu
Apr 29, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Elena I Deryugina, James P Quigley
Apr 29, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yi-Hsien HsiehJen-Pi Tsai
Oct 3, 2015·Oncotarget·Marina Trombetta-LimaMari Cleide Sogayar
Oct 16, 2015·Current Vascular Pharmacology·Jaime GutiérrezLuis Sobrevia
Jan 7, 2016·Annals of Translational Medicine·Jiezhong ChenChen Chen
Jun 2, 2016·Methods in Molecular Biology·Siddavaram Nagini, Jaganathan Kowshik
Oct 4, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Kamdeo K PramanikRajakishore Mishra

❮ Previous
Next ❯

Citations

Dec 1, 2017·Molecular Biology Reports·Ghedeir M AlshammariThirunavukkarasu Chinnasamy
Jul 28, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Yulong MaoJinhua Zuo
Sep 9, 2018·Molecular Biology Reports·Satabdi RautrayA Usha Rajananthini
Mar 20, 2021·Journal of Medicinal Chemistry·Siddavaram NaginiRajakishore Mishra
Dec 22, 2021·Phytotherapy Research : PTR·Luis M Ruiz-ManriquezSujay Paul
May 8, 2019··Hayk GevorgyanAnatol Khilo

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
xenograft
nuclear translocation
PCR

Software Mentioned

Total Lab
SITEMAP

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.