β,β-Dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling pathway in vitro and in vivo

Shao, Zengwu; Zhang, Yuanyuan; Fan, Yingying; Jin, Shaoju; Yan, Jin; Zheng, Xiaoliang; Chen, Jian; Xiong, Yan; Zhou, Liming

doi:10.1016/j.bcp.2012.05.013

Cited by 16 publications

(11 citation statements)

References 22 publications

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“…Previous investigations have also demonstrated that 1 affected the amount of melanoma cells in the S- (SBcl2 and WM35 cells) or G2/M-phase (WM9 and WM164 cells) [ 8 ]. Also shikonin led to a cell cycle arrest in different cancer cell lines and immortalized human keratinocytes [ 41 , 42 , 43 , 44 , 45 ]. Therefore, the effects of 6 on cell cycle distribution were investigated ( Figure 4 B–D).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells

et al. 2018

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Despite much research in the last centuries, treatment of malignant melanoma is still challenging because of its mostly unnoticeable metastatic spreading and aggressive growth rate. Therefore, the discovery of novel drug leads is an important goal. In a previous study, we have isolated several shikonin derivatives from the roots of Onosma paniculata Bureau & Franchet (Boraginaceae) which evolved as promising anticancer candidates. β,β-Dimethylacrylshikonin (1) was the most cytotoxic derivative and exhibited strong tumor growth inhibitory activity, in particular, towards melanoma cells. In this study, we synthesized eighteen novel shikonin derivatives in order to obtain compounds which exhibit a higher cytotoxicity than 1. We investigated their cytotoxic potential against various melanoma cell lines and juvenile skin fibroblasts. The most active compound was (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl cyclopropylacetate (cyclopropylacetylshikonin) (6). It revealed significant stronger tumor growth inhibitory activity towards two melanoma cell lines derived from metastatic lesions (WM164 and MUG-Mel2). Further investigations have shown that 6 induced apoptosis caspase-dependently, increased the protein levels of cleaved PARP, and led to double-stranded DNA breaks as shown by phosphorylation of H2AX. Cell membrane damage and cell cycle arrest were not observed.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells

et al. 2018

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“…In addition, extensive reports have shown that shikonin and its derivatives exhibit antitumor activity against a variety of human cancers, and DMAS is one of the most effective agents. For example, DMAS exerted antitumor activity against human gastric cancer cells via Notch-1 downregulation [7] . Moreover, DMAS showed a significant toxicological effect on hepatocellular carcinoma cells through increased caspase-3 activity [8] .…”

Section: Introductionmentioning

confidence: 99%

β, β-Dimethylacrylshikonin induces mitochondria-dependent apoptosis of human lung adenocarcinoma cells in vitro via p38 pathway activation

Wang

2014

Acta Pharmacol Sin

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“…The treatment of chronic myelogenous leukemia K562 cells ( 5 ), human prostate cancer PC-3 cells ( 20 ), melanoma cells ( 6 ) and osteosarcoma cells ( 21 ) with shikonin induced apoptosis through increased caspase-3 activity. Our previous studies also showed that DA induced apoptosis in hepatocellular carcionoma SMMC-7721 cells ( 7 ) and gastric cancer SGC-7901 cells ( 22 ). To further investigate the underlying mechanisms of its antiproliferative effects, the present study investigated the expression of apoptosis-related proteins and the activity of the NF-κB pathway in DA-treated MCF-7 cells.…”

Section: Discussionmentioning

confidence: 73%

Apoptosis induced by β,β-dimethylacrylshikonin is associated with Bcl-2 and NF-κB in human breast carcinoma MCF-7 cells

Xiong

Zhang

et al. 2013

Oncology Letters

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β,β-dimethylacrylshikonin (DA) is a natural naphthoquinone derivative compound of Lithospermum erythrorhizon with various biological activities. The present study aimed to investigate the inhibitory effects and underlying mechanisms of DA in human breast carcinoma MCF-7 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DA inhibited the proliferation of MCF-7 cells in a dose- and time-dependent manner. The half maximal inhibitory concentration of DA with regard to the proliferation of MCF-7 cells was 0.050±0.016 mM. The characteristics of cell apoptosis, including cell shrinkage, nuclear pyknosis and chromatin condensation, were all observed in DA-treated cells. DA decreased the expression levels of Bcl-2 and increased the expression of Bax and caspase-3 compared with those in the control. DA inhibited the activity of the nuclear factor (NF)-κB pathway, by downregulating the expression of the p65 subunit, and inhibited the Iκb phosphorylation. DA inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-κB pathway.

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β,β-Dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling pathway in vitro and in vivo

Cited by 16 publications

References 22 publications

Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells

Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells

β, β-Dimethylacrylshikonin induces mitochondria-dependent apoptosis of human lung adenocarcinoma cells in vitro via p38 pathway activation

Apoptosis induced by β,β-dimethylacrylshikonin is associated with Bcl-2 and NF-κB in human breast carcinoma MCF-7 cells

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