Activity guided isolation and modification of juglone from Juglans regia as potent cytotoxic agent against lung cancer cell lines

Zhang, Xuebang; Zou, Changlin; Duan, Yuxia; Wu, Fang; Li, Gang

doi:10.1186/s12906-015-0920-0

Cited by 50 publications

(30 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…as STAT3 signaling inhibitors [14] and found that 2-methoxystypandrone inhibited both STAT3 and NF-κB pathways dramatically by inhibiting Janus kinase 2 (JAK2) and IκB kinase (IKK) [15]. Juglone analogues have been isolated from numerous medicinal plants as active constituents, which exhibited many biological activities such as anti-viral, anti-bacterial, anti-inflammatory, and anti-cancer activities [16, 17]. Because of an interest in juglone analogues with STAT3 pathway inhibitory activities, the EtOAc extract of the roots of P. cuspidatum was re-examined and a novel juglone analogue 2-ethoxystypandrone (1) along with seven known compounds (2–8) were isolated.…”

Section: Introductionmentioning

confidence: 99%

2-Ethoxystypandrone, a novel small-molecule STAT3 signaling inhibitor from Polygonum cuspidatum, inhibits cell growth and induces apoptosis of HCC cells and HCC Cancer stem cells

Zhang

Chen

et al. 2019

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundSignal transducer and activator of transcription 3 (STAT3) is an oncogene constitutively activated in hepatocellular carcinoma (HCC) cells and HCC cancer stem cells (CSCs). Constitutively activated STAT3 plays a pivotal role in holding cancer stemness of HCC CSCs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance. Therefore, STAT3 has been validated as a novel anti-cancer drug target and the strategies targeting HCC CSCs may bring new hopes to HCC therapy. This study aimed to isolate and identify small-molecule STAT3 signaling inhibitors targeting CSCs from the ethyl acetate (EtOAc) extract of the roots of Polygonum cuspidatum and to evaluate their in vitro anti-cancer activities.MethodsThe chemical components of the EtOAc extract and the subfractions of P. cuspidatum were isolated by using various column chromatographies on silical gel, Sephadex LH-20, and preparative HPLC. Their chemical structures were then determined on the basis of spectroscopic data including NMR, MS and IR analysis and their physicochemical properties. The inhibitory effects of the isolated compounds against STAT3 signaling were screened by a STAT3-dependent luciferase reporter gene assay. The tyrosine phosphorylation of STAT3 was examined by Western Blot analysis. In vitro anti-cancer effects of the STAT3 pathway inhibitor were further evaluated on cell growth of human HCC cells by a MTT assay, on self-renewal capacity of HCC CSCs by the tumorsphere formation assay, and on cell cycle and apoptosis by flow cytometry analysis, respectively.ResultsThe EtOAc extract of the roots of P. cuspidatum was investigated and a novel juglone analogue 2-ethoxystypandrone (1) along with seven known compounds (2–8) was isolated. Among the eight isolated compounds 1–8, 2-ethoxystypandrone was a novel and potent STAT3 signaling inhibitor (IC50 = 7.75 ± 0.18 μM), and inhibited the IL-6-induced and constitutive activation of phosphorylation of STAT3 in HCC cells. Moreover, 2-ethoxystypandrone inhibited cell survival of HCC cells (IC50 = 3.69 ± 0.51 μM ~ 20.36 ± 2.90 μM), blocked the tumorspheres formation (IC50 = 2.70 ± 0.28 μM), and induced apoptosis of HCC CSCs in a dose-dependent manner.ConclusionA novel juglone analogue 2-ethoxystypandrone was identified from the EtOAc extract of the roots of P. cuspidatum and was demonstrated to be a potent small-molecule STAT3 signaling inhibitor, which strongly blocked STAT3 activation, inhibited proliferation, and induced cell apoptosis of HCC cells and HCC CSCs. 2-Ethoxystypandrone as a STAT3 signaling inhibitor might be a promising lead compound for further development into an anti-CSCs drug.Electronic supplementary materialThe online version of this article (10.1186/s12906-019-2440-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

2-Ethoxystypandrone, a novel small-molecule STAT3 signaling inhibitor from Polygonum cuspidatum, inhibits cell growth and induces apoptosis of HCC cells and HCC Cancer stem cells

Zhang

Chen

et al. 2019

BMC Complement Altern Med

View full text Add to dashboard Cite

show abstract

“…Juglone, a naphthoquinone, isolated from Juglans regia is a potential cytotoxic compound against human lung cancer cell lines, and the electron-withdrawing groups at the ortho position of the R moiety of juglone seem to be necessary for the enhancement of its cytotoxic activity [24].…”

Section: Quinonoids Inhibit Proliferation and Induce Apoptosismentioning

confidence: 99%

Quinonoids: Therapeutic Potential for Lung Cancer Treatment

Ying

Chen

et al. 2020

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer-related deaths worldwide. Owing to its high incidence and mortality, the development and discovery of novel anticancer drugs is of great importance. In recent years, many breakthroughs have been achieved in the search for effective anticancer substances from natural products. Many anticancer drugs used clinically and proven to be effective are derived from natural products. Quinonoids, including naphthoquinones, phenanthrenequinones, benzoquinones, and anthraquinones, constitute a large group of natural bioactive compounds that widely exist in higher and lower plant species. Given that most of these compounds possess anticancer effects, they are applied in many cancer studies, especially in lung cancer research. They can promote apoptosis, induce autophagy, and inhibit proliferation, angiogenesis, and cell invasion and migration. Some drugs can enhance anticancer effects when combined with other drugs. Thus, quinonoids have broad application prospects in the treatment of lung cancer. Here, we summarize the previous studies on the antilung cancer activities of quinonoids together with their underlying mechanisms and analyze the common research targets with different effects so as to provide references for the discovery of quinonoids against lung cancer.

show abstract

“…Juglone ( Figure 1 ) is a member of this family, acting as a growth-stunting agent [ 136 ] and apoptosis inducer. It exhibits antitumour activity on many types of tumours, such as breast [ 92 , 93 , 94 , 95 , 137 ], skin [ 99 , 100 , 137 ], glial cells [ 109 , 110 , 111 , 135 , 138 ], lung [ 137 , 138 ], prostate [ 105 , 106 , 107 , 137 ], pancreas [ 97 ], bladder [ 108 ], stomach [ 98 ], cervix [ 102 , 103 , 139 , 140 ], ovary [ 104 ], and blood [ 113 , 114 ]. For some of them, the mechanism of action has been investigated.…”

Section: Anticancer Activitymentioning

confidence: 99%

Natural Products to Fight Cancer: A Focus on Juglans regia

Catanzaro

Greco

Potenza

et al. 2018

Toxins

View full text Add to dashboard Cite

Even if cancer represents a burden for human society, an exhaustive cure has not been discovered yet. Low therapeutic index and resistance to pharmacotherapy are two of the major limits of antitumour treatments. Natural products represent an excellent library of bioactive molecules. Thus, tapping into the natural world may prove useful in identifying new therapeutic options with favourable pharmaco-toxicological profiles. Juglans regia, or common walnut, is a very resilient tree that has inhabited our planet for thousands of years. Many studies correlate walnut consumption to beneficial effects towards several chronic diseases, such as cancer, mainly due to the bioactive molecules stored in different parts of the plant. Among others, polyphenols, quinones, proteins, and essential fatty acids contribute to its pharmacologic activity. The present review aims to offer a comprehensive perspective about the antitumour potential of the most promising compounds stored in this plant, such as juglanin, juglone, and the ellagitannin-metabolites urolithins or deriving from walnut dietary intake. All molecules and a chronic intake of the fruit provide tangible anticancer effects. However, the scarcity of studies on humans does not allow results to be conclusive.

show abstract

Activity guided isolation and modification of juglone from Juglans regia as potent cytotoxic agent against lung cancer cell lines

Cited by 50 publications

References 32 publications

2-Ethoxystypandrone, a novel small-molecule STAT3 signaling inhibitor from Polygonum cuspidatum, inhibits cell growth and induces apoptosis of HCC cells and HCC Cancer stem cells

2-Ethoxystypandrone, a novel small-molecule STAT3 signaling inhibitor from Polygonum cuspidatum, inhibits cell growth and induces apoptosis of HCC cells and HCC Cancer stem cells

Quinonoids: Therapeutic Potential for Lung Cancer Treatment

Natural Products to Fight Cancer: A Focus on Juglans regia

Contact Info

Product

Resources

About