Naphthoquinones from Onosma paniculata Induce Cell-Cycle Arrest and Apoptosis in Melanoma Cells

Abstract

Activity-guided fractionation of a petroleum ether-soluble extract of the roots of Onosma paniculata, which has been shown to affect the cell cycle and to induce apoptosis in melanoma cells, led to the isolation of several shikonin derivatives, namely, β-hydroxyisovalerylshikonin (1), acetylshikonin (2), dimethylacrylshikonin (3), and a mixture of α-methylbutyrylshikonin and isovalerylshikonin (4+5). All compounds exhibited strong cytotoxicity against eight cancer cell lines and MRC-5 lung fibroblasts, with 3 found to possess the most potent cytotoxicity toward four melanoma cell lines (SBcl2, WM35, WM9, and WM164). Furthermore, 3 and the mixture of 4+5 were found to interfere with cell-cycle progression in these cell lines and led to an increasing number of cells in the subG1 region as well as to caspase-3/7 activation, indicating apoptotic cell death.

Acetylshikonin inhibits growth of oral squamous cell carcinoma by inducing apoptosis

“…Consistent with the present data, recent studies have observed the suppressive effects of acetylshikonin on the cell growth of several types of cancers, such as gastric carcinoma, melanoma, and colon cancer (Kretschmer et al, 2012;Rajasekar et al, 2012;Zeng et al, 2009). Although a study of the neuronal cell lines reported that acetylshikonin protected those cells from apoptosis (Wang et al, 2013), this neuroprotective role was limited to apoptotic cell death by oxidative stress.…”

Antibacterial and cytotoxic activities of naphthoquinone pigments from Onosma visianii Clem

“…1)). Structural identification of all isolated naphthoquinones was performed by spectroscopic techniques listed in experimental part, as well as by comparison of obtained data with those previously published in the literature (Kretschmer et al, 2012[14]; Ozgen et al, 2004[20]; Albreht et al, 2009[1]; Wang et al, 2015[26]; Zhou et al, 2010[27]). Among isolated compounds, 5,8- O -dimethyl isobutyrylshikonin ( 6 ) was found in nature for the first time.…”

“…Among 1500 tested quinones, about 150 compounds showed strong in vivo activity against W256 in rats and P388 lymphoid leukemia in mice, as well as significant in vitro potency toward KB cells and CCRF-CEM leukemia cells (Papageorgiou et al, 1999[23]). On the other hand, isolated quinones demonstrated significant in vitro potency toward KB cells, CCRF-CEM leukemia cells, as well as some melanoma cell lines (Papageorgiou et al, 1999[23]; Kretschmer et al, 2012[14]). To determine whether cytotoxicity induced by naphthoquinones was due to apoptosis or cell cycle arrest, the cells were stained with fluorescent dyes and analyzed on flow cytometer.…”

Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib

“…Shikonin and alkannin derivatives were isolated and identified from plants as described. 19,20 The chemical structures are shown in Figure 1a. Stock solutions were prepared in DMSO and stored at 220 C and were diluted to the final concentration in fresh media before each experiment.…”