Abstract
Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3–17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1–17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer.
Highlights
Juglans sinensis Dode (Juglandaceae) is a deciduous tree indigenous to Eastern Asia and commonly known as the walnut tree
Sesquiterpenes and triterpenes isolated from the leaves and twigs of J. sinensis inhibited the proliferation of immortalized rat hepatic stellate cells through apoptosis [1]; the mechanism of action of the anti-proliferation activity of the phenolic compounds of J. sinensis has not been investigated in detail
17 phenolic compounds 1–17 were isolated from the bark of J. sinensis; their cytotoxic activities were tested against diverse human cancer cells
Summary
Juglans sinensis Dode (Juglandaceae) is a deciduous tree indigenous to Eastern Asia and commonly known as the walnut tree. Previous phytochemical reports on this plant identified terpenoids, diarylheptanoids, naphthalenones, flavonoids, and phenolic compounds [1,2,3,4], which were related to its cytotoxic [1], neuroprotective [2], hepatic fibrosis inhibitory [3], and hepatoprotective [4] activities. In previous reports on the anticancer effects of Juglans species, the extracts of root barks, fruits, or seeds of J. regia showed anti-proliferative activity against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MDA-MB-231 human breast cancer cells [8,9,10]; the extract of seeds of. Sesquiterpenes and triterpenes isolated from the leaves and twigs of J. sinensis inhibited the proliferation of immortalized rat hepatic stellate cells through apoptosis [1]; the mechanism of action of the anti-proliferation activity of the phenolic compounds of J. sinensis has not been investigated in detail. We describe the separation and structure elucidation of such cytotoxic compounds, and we evaluated their anti-proliferative and apoptotic activity to study mechanism of the cytotoxicity of these compounds in human cancer cells
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