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. 2019 Aug 27;516(3):733-738.
doi: 10.1016/j.bbrc.2019.06.123. Epub 2019 Jun 26.

Potential anti-neuroblastoma agents from Juniperus oblonga

Yilin Qiao  1 , Nathan K Sunada  2 , Alyssa E Hatada  2 , Ingo Lange  2 , Manana Khutsishvili  3 , Valida Alizade  4 , Daniel Atha  5 , Dana-Lynn Ko'omoa-Lange  2 , Robert P Borris  6
Affiliations

Potential anti-neuroblastoma agents from Juniperus oblonga

Yilin Qiao et al. Biochem Biophys Res Commun. .

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 IC50 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.

Keywords: Apoptosis; Calcium signaling; Juniperus oblonga; MYCN2 amplification; Neuroblastoma.

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Figures

Fig. 1
Fig. 1
Structures of compounds 1-3 from Juniperus oblonga
Fig. 2
Fig. 2
Dose-dependent effects of compounds 1, 2, 3 in M2(−) and M2(+) cells (a): Compound 1, (b): Compound 2, (c): Compound 3
Fig. 3
Fig. 3
PARP cleavage and pCNA level in M2(−) and M2(+) cells treated with compounds 1, 2 and 3
Fig. 4
Fig. 4
Intracellular free calcium levels in M2(+) cells with compound 1
See this image and copyright information in PMC

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