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Hesperidin inhibits insulin-induced phosphoinositide 3-kinase/Akt activation in human pre-B cell line NALM-6


1 Department of Basic Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Biochemistry, Fasa University of Medical Sciences, Fasa, Iran
4 Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
5 Department of Clinical Nutrition and Dietetic, National Institute and Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6 Department of Clinical Nutrition and Dietetic, National Institute and Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences; Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Correspondence Address:
Sayed Hossein Davoodi,
Cancer Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 1989934148, Tehran, Iran, and Department of Clinical Nutrition and Dietetic, National Institute and Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, P.O. Box 19395 4741, Tehran
Iran
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Source of Support: None, Conflict of Interest: None

 > Abstract 

Context: It has been shown that hesperidin induces apoptosis in NALM-6 cells through inhibition of nuclear factor-kappa B (NF-kB) activation.
Aims: To investigate the effect of hesperidin on inhibition of NF-kB activation through blocking phosphoinositide 3-kinase (PI3K)/Akt pathway as a main target in cancer treatment, in NALM-6 cells.
Materials and Methods: NALM-6 cells were incubated with two concentrations of hesperidin (25, 50 mM) in the presence or absence of insulin (100 nM), as a potent activator of Akt. The cytotoxic activity of hesperidin was determined by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptotic death was measured by ELISA test using cell death detection ELISA Plus kit. To assay the effect of hesperidin on Akt pathway, the phosphorylation levels of Akt, inhibitor of kappa B alpha (IkBa), and glycogen synthase kinase-3 beta (GSK-3b) and expression level of IkB kinase alpha (IKKa) were determined by Western blot analysis.
Results: Hesperidin (both concentrations) significantly reduced cells survival in the presence and absence of insulin compared to untreated cells in a time-dependent manner (P < 0.05). Hesperidin also significantly increased apoptosis in NALM-6 cells even in hyperinsulinemia condition (P < 0.0001). Hesperidin inhibited insulin-induced phosphorylation and activation of Akt, IkBa, and GSK-3b and decreased expression of IKKa.
Conclusion: The results of this study demonstrated that cytotoxic and proapoptotic actions of hesperidin are partly mediated through the suppression of PI3K3/Akt/IKK signaling pathway. So, hesperidin might act as a chemotherapeutic agent by targeting cell survival pathways.

Keywords: Apoptosis, glycogen synthase kinase-3 beta, hesperidin, inhibitor of kappa B, inhibitor of kappa B kinase, nuclear factor-kappa B, phosphoinositide 3-kinase/Akt



How to cite this URL:
Shahbazi R, Cheraghpour M, Homayounfar R, Nazari M, Nasrollahzadeh J, Davoodi SH. Hesperidin inhibits insulin-induced phosphoinositide 3-kinase/Akt activation in human pre-B cell line NALM-6 . J Can Res Ther [Epub ahead of print] [cited 2017 Oct 18]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=157323

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