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Potential anti-neuroblastoma agents from Juniperus oblonga.

Authors :: Qiao Y
Sunada NK
Hatada AE
Lange I
Khutsishvili M
Alizade V
Atha D
Ko'omoa-Lange DL
Borris RP
Source :: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 Aug 27; Vol. 516 (3), pp. 733-738. Date of Electronic Publication: 2019 Jun 26.
Publication Year :: 2019
Abstract: Neuroblastoma (NB) is a neuroendocrine tumor derived from neural crest cells. Approximately 90% of cases occur in children less than 5 years old. The amplification of MYCN correlates with high-risk neuroblastoma and patients with MYCN amplified showed poorer prognosis than those without MYCN amplification. In this study, three compounds isolated from Juniperus oblonga showed anti-proliferative activity against NB cell lines with and without tetracycline inducible MYCN over-expression which were identified as (-)-deoxypodophyllotoxin (1), (-)-matairesinol (2) and (+)-isocupressic acid (3). The effects of compounds 2 and 3 in NB cells included a decrease in NB cell viability and induction of apoptosis. Compound 1 was more effective in NB cells over-expressing MycN. Compound 1 also showed almost 2-fold induction of intracellular free calcium levels in M2(+) cells, which may indicate a different mechanism of action for this compound. Cytotoxicity studies against the human embryonic kidney cell (HEK-293) showed compounds 1, 2 and 3 were ineffective in the non-cancer cells at concentrations approximating their IC <subscript>50</subscript> against the NB cell lines. These results may lead to safer and more effective treatment options for NB patients especially for those with high-risk NB.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)