Moringin from Moringa Oleifera Seeds Inhibits Growth, Arrests Cell-Cycle, and Induces Apoptosis of SH-SY5Y Human Neuroblastoma Cells through the Modulation of NF-κB and Apoptotic Related Factors.

Santa Cirmi,Nadia Ferlazzo,Michele Navarra,Laura Musumeci,Alessia Bramanti,Emanuela Mazzon,Agnese Gugliandolo

doi:10.3390/ijms20081930

Abstract

In the last decades, glucosinolates (GLs), precursors of isothiocyanates (ITCs), have been studied mostly for their chemopreventive and chemotherapeutic properties. The aim of our research was to study the antiproliferative effect of 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (glucomoringin; GMG) bioactivated by myrosinase enzyme to form the corresponding isothiocyanate 4-(α-L-rhamnopyranosyloxy) benzyl C (moringin) in SH-SY5Y human neuroblastoma cells. We found that moringin significantly reduced SH-SY5Y cell growth in a time and concentration-dependent (p < 0.05, 0.01, and 0.001 vs. ctrl, after treatment with 16.4 µM moringin for 24, 48, and 72 h, respectively) manner through a mechanism involving the activation of apoptotic machinery. In addition, it altered the normal progression of cells through the cell cycle, increasing the cell population in both G2 and S phases, as well as decreasing that in the G1 phase. Studying the drug mechanism of action, we found that moringin was able to increase the expression of p53, p21, and Bax at both the protein and transcriptional level. Moreover, exposure of SH-SY5Y cells to moringin significantly increased the gene expression of both caspase 3 and 9 and enhanced their cleavage, thereby initiating an intrinsic apoptotic cascade. Finally, moringin inhibited nuclear translocation of NF-κB. Our study demonstrates the ability of moringin to reduce the growth of SH-SY5Y cells and reveals its mechanism of action, suggesting its promising role as an anticancer drug.

Highlights

Moringa oleifera Lam. is the most widely distributed plant of the Moringaceae family that grows widely in many tropical and subtropical countries [1]
Due to the role of ITCs in cancer management, the aim of our study was to evaluate the antiproliferative effect of moringin on SH-SY5Y human neuroblastoma cells, and its molecular mechanisms of action
MTT data were established by counting cells in a Neubauer hemocytometer chamber after 24, 48, and 72 h treatment with moringin (Figure 1D)

Summary

Introduction

Moringa oleifera Lam. is the most widely distributed plant of the Moringaceae family that grows widely in many tropical and subtropical countries [1]. The majority of its medicinal and nutritional properties have been ascribed to some parts of the plant, such as seeds, flowers, roots, leaves and bark, which are used in traditional medicine for the management of several diseases [3]. Extracts of different parts of Moringa oleifera have been recognized as anti-inflammatory, anti-bacterial, anti-cancer, and hepatoprotective remedies [4,5]. GLs have three moieties: a β-thioglucose moiety, a sulfonated oxime moiety, and a variable aglycone side chain derived from an α-amino acid [6]. M. oleifera possesses many unusual GLs with atypical characteristics due to a second saccharide residue in the aglyconic side chain [6,7]

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Results