Xanthone Derivatives as Potential Anti-cancer Drugs

Lin, Chun‐Nan; Liou, Shiou-Jyh; Lee, Tai‐Hua; Chuang, Yin-Ching; Won, Shen‐Jeu

doi:10.1111/j.2042-7158.1996.tb05970.x

Cited by 63 publications

(24 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DMXAA induces apoptosis of tumor vascular endothelial cells and cytokine production, leading to tumor vascular collapse (13). As we previously reported, a series of oxygenated xanthones and [3-(dialkylamino)-2-hydroxypropoxy]xanthones have been prepared and tested for anticancer activity (14). 2,6-Di(2,3-epoxypropoxy)xanthone was chosen for further study, and the mechanism of action is proposed to involve a selective downregulation of Ras (15).…”

mentioning

confidence: 99%

EPOX Inhibits Angiogenesis by Degradation of Mcl-1 through ERK Inactivation

Sun

Tsai

Pan

et al. 2009

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Antiangiogenic therapy is considered as an effective strategy for controlling the growth and metastasis of tumors. Among a myriad of biological activities described for xanthone derivatives, the anticancer activity is quite remarkable, but the molecular mechanism is not clearly resolved. In the present study, we investigated the antiangiogenic mechanism of 3,6-di(2,3-epoxypropoxy)xanthone (EPOX), a novel Mcl-1 targeting drug. Experimental Design: To evaluate the antiangiogenic activity of EPOX, we did cell viability, cell cycle, tube formation assay in vitro, and Matrigel plug assay in vivo. To evaluate the effect of EPOX on the endothelial signaling pathway, we did immunoblotting, immunoprecipitation, and immunofluorescence analysis. Intracellular glutathione levels were determined with the use of monochlorobimane, a glutathione-specific probe. Results: EPOX induced endothelial cell apoptosis in association with proteasomedependent Mcl-1 degradation. Down-regulation of Mcl-1 resulted in an increase in Mcl-1-free Bim, activation of Bax, and then signaling of mitochondria-mediated apoptosis. Additionally, glutathione depletion and extracellular signal-regulated kinase (ERK) inactivation was observed in EPOX-treated cells. Glutathione supplementation reversed the inhibitory effects of EPOX on ERK, which increases the phosphorylation of Mcl-1 at T 163 . Overexpression of mitogen-activated protein/ERK kinase (MEK) partially reversed the effect of EPOX on Mcl-1 dephosphorylation, ubiquitination, and degradation, further implicating ERK in the regulation of Mcl-1 stability. Conclusions: This study provides evidence that EPOX induces glutathione depletion, ERK inactivation, and Mcl-1 degradation on endothelial cells, which leads to inhibition of angiogenesis. Our results suggest that EPOX is a novel antiangiogenic agent, making it a promising lead compound for further development in the treatment of angiogenesisrelated pathologies.

show abstract

mentioning

confidence: 99%

EPOX Inhibits Angiogenesis by Degradation of Mcl-1 through ERK Inactivation

Sun

Tsai

Pan

et al. 2009

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lin and coworkers report that 2,3-epoxypropoxy substituted xanthones have efficiently inhibited growth of cancer cells and xanthone possessing two 2,3-epoxypropoxy groups at 3 and 5 position showed most active anticancer activity in the series prepared. 12,13) The structural features inherent in xanthone derivatives make us aware that the substitute groups in xanthones may have significant influence on the biological activity. With this rational in mind, we have investigated the binding mode on the interactions of isoeuxanthone (1,6-dihydroxyxanthone) (1) and its piperidinyl derivative (1-hydroxy-6-(2-(1-piperidinyl) ethoxy) xanthone) (2) (shown in Fig.…”

mentioning

confidence: 99%

Antitumor Activity and DNA-Binding Investigations of Isoeuxanthone and Its Piperidinyl Derivative

Wang

Wei

Yan

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The binding mode and affinity of isoeuxanthone (1,6-dihydroxyxanthone) (1) and its piperidinyl derivative (1-hydroxy-6-(2-(1-piperidinyl)ethoxy)xanthone) (2) with calf thymus DNA were studied using absorption spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and viscosity measurements. Results indicate that the two xanthones can intercalate into the DNA base pairs by the plane of xanthone ring and the binding affinity of the piperidinylethoxy substituted xanthone 2 is stronger than 1. In addition, the cytotoxic effects of both compounds were evaluated with the human cervical cancer cell line (HeLa) and human hepatocellular liver carcinoma cell line (HepG2) using acid phosphatase assay. Analyses show that the piperidinylethoxy substituted xanthone exhibits more effective cytotoxic activity than isoeuxanthone against the two cancer cells. The effects on the inhibition of tumor cells in vitro agree with the studies of DNAbinding.

show abstract

“…Coumarin was identified in all extracts. Studies in various tumor cell lines have pointed to coumarin and its derivatives as potential substances for cancer treatment [14][15][16][17][18]. Other compounds with antitumor activity were identified in the extracts analyzed: curcumene, psoralen, kaurenoic acid, scopoletin, o-coumaric acid, pinene [19][20][21][22][23].…”

Section: Resultsmentioning

confidence: 99%

Cytotoxicity effect of ethanolic extract of Mikania glomerata against A549 human lung cancer cell line

Sarojini

Vinayagam

Senthilkumaar

2016

Int J of Adv in Sci Res

View full text Add to dashboard Cite

The genus Mikania is the largest of its kind in the family Eupatorieae (Asteraceae), with more than 430 species concentrated mainly in the tropical regions, among which, Mikania glomerata is a most common herb generally employed in the treatment of respiratory disorders. The Milania glomerata plant leaf extracts were used for anticancer study against A549 human lung cancer cell line. The solid -liquid extraction method has been employed to prepare the ethanol extract of Mikania glomerata through soxhelt apparatus method. To check the anti-proliferative effect of this extract, the extract chosen was tested for cell viability on the lung cancer cells A549 in different concentrations. Cell viability was evaluated by MTT assay for 24 hour and 48 hours. The LD 50 value was calculated for the level of cell death and its effectiveness. The dose-dependent manner plays an important role in the treatment of lung cancer cell lines. The present study suggests that Mikania glomerata may be used as an alternative anticancer agent and further research is needed to improve the effectiveness.

show abstract

Xanthone Derivatives as Potential Anti-cancer Drugs

Cited by 63 publications

References 12 publications

EPOX Inhibits Angiogenesis by Degradation of Mcl-1 through ERK Inactivation

EPOX Inhibits Angiogenesis by Degradation of Mcl-1 through ERK Inactivation

Antitumor Activity and DNA-Binding Investigations of Isoeuxanthone and Its Piperidinyl Derivative

Cytotoxicity effect of ethanolic extract of Mikania glomerata against A549 human lung cancer cell line

Contact Info

Product

Resources

About