β-Eudesmol suppresses tumour growth through inhibition of tumour neovascularisation and tumour cell proliferation

Ma, Enlong; Li, Yanchun; Tsuneki, Hiroshi; Xiao, Jingjie; Xia, Mingyu; Wang, Minwei; Kimura, Ikuko

doi:10.1080/10286020701394332

Cited by 56 publications

(45 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, β‐eudesmol may inhibit angiogenesis by suppressing CREB and ERK signalling pathways. In fact, β‐eudesmol significantly inhibited angiogenesis in subcutaneously implanted Matrigel plugs in mice and in adjuvant‐induced granuloma in mice , as well as the growth of H(22) and S(180) mouse tumour in vivo . However, the anti‐angiogenic potential of α‐ or γ‐eudesmol was not investigated.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Eudesmol Isomers Induce Caspase‐Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

Bomfim

Ferraz

Carvalho

et al. 2013

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Eudesmols are naturally occurring sesquiterpenoid alcohols that present cytotoxic effect to cancer cells. Herein, all eudesmol isomers displayed cytotoxicity to different tumour cell lines. a-Eudesmol showed IC 50 values ranging from 5.38 AE 1.10 to 10.60 AE 1.33 lg/mL for B16-F10 and K562 cell lines, b-eudesmol showed IC 50 values ranging from 16.51 AE 1.21 to 24.57 AE 2.75 lg/mL for B16-F10 and HepG2 cell lines, and c-eudesmol showed IC 50 values ranging from 8.86 AE 1.27 to 15.15 AE 1.06 lg/mL for B16-F10 and K562 cell lines, respectively. In addition, in this work, we studied the mechanisms of cytotoxic action of eudesmol isomers (a-, b-and c-eudesmol) in human hepatocellular carcinoma HepG2 cells. After 24-hr incubation, HepG2 cells treated with eudesmol isomers presented typical hallmarks of apoptosis, as observed by morphological analysis in cells stained with haematoxylin-eosin and acridine orange/ethidium bromide. None of eudesmol isomers caused membrane disruption at any concentration tested. Moreover, eudesmol isomers induced loss of mitochondrial membrane potential and an increase in caspase-3 activation in HepG2 cells, suggesting the induction of caspase-mediated apoptotic cell death. In conclusion, the eudesmol isomers herein investigated are able to reduce cell proliferation and to induce tumour cell death by caspase-mediated apoptosis pathways.Several studies have demonstrated that natural products and/or natural product structures continued to play a highly significant role in drug discovery and development process. In the case of approved therapeutic agents (01/1981-12/2010), only 20.2% of the total number of small-molecule anticancer drugs is classifiable into the synthetic category [1].Some studies have reported cytotoxic activity for plants belonging to the genus Guatteria of the Annonaceae plant family [2][3][4][5]. Our research group demonstrated that the leaf essential oil of Guatteria friesiana possesses in vitro and in vivo antitumour actions, without substantial systemic toxicity [5]. The main components identified in G. friesiana essential oil were eudesmol isomers (a-, b-and c-eudesmol; fig. 1 [15]. These three eudesmol isomers have been also reported previously as cytotoxic agents, displaying cytotoxicity to several human tumour cell lines [5,8,9,16,17]. Moreover, other plant species that contain eudesmol isomers also present cytotoxic activity [18,19]. In addition, Li et al. [20] reported that b-eudesmol induces c-Jun N-terminal kinases (JNK)-dependent apoptosis through the mitochondrial pathway in HL60 cells; however, the mechanism of cytotoxicity of aor c-eudesmol has not been investigated. Therefore, in the present work, we investigated the cytotoxic mechanism of eudesmol isomers (a-, b-and c-eudesmol) in human hepatocellular carcinoma HepG2 cells. Materials and MethodsEudesmols isolation. Guatteria friesiana leaves were collected at the Federal University of Amazonas (UFAM), Manaus, AM, Brazil, in January 2008. A voucher specimen (no. 7341) was deposited in the Herbar...

show abstract

Section: Discussionmentioning

confidence: 99%

“…In addition, Ma et al . showed that β‐eudesmol blocked the phosphorylation of cAMP response element binding protein (CREB) induced by VEGF in HUVEC. Therefore, β‐eudesmol may inhibit angiogenesis by suppressing CREB and ERK signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

Eudesmol Isomers Induce Caspase‐Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

Bomfim

Ferraz

Carvalho

et al. 2013

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…Recently, researches on effectiveness of β-eudesmol to blood vessels on the nervous system and also antitumor and anticancer effects have been largely in progress. Apoptotic effect through neovascular control effect of β-eudesmol has been reported (Ikeda and Nagase 2002;Ma et al 2008). And it has been proved that β-eudesmol has apoptotic effect through caspase-3 via caspase-9 caused by cytochrome in HL-60 cells (Hoang et al 2010), c-Jun N-terminal kinase (JNK)-dependent apoptotic effect through mitochondria passage in HL-60 cells (Li et al 2013), and anticancer effects in the experiment of nude mouse to whom it implanted through the method of heterotransplantation of human cholangiocarcinoma (Plengsuriyakarn et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Looking at existing studies on β-eudesmol, there have been reports about medical and pharmacologic researches on its anti-inflammation, antimutagenicity, nervous system stabilization, vasodilator, antitumor, and anticancer effects (Li et al 2013;Miyazawa et al 1996;Kimura et al 1991;Chiou and Chang 1992;Satoh et al 1992;Chiou et al 1995;Obara et al 2002;Lim and Kee 2005;Seo et al 2011;Ikeda and Nagase 2002;Ma et al 2008;Plengsuriyakarn et al 2015). However, research on the mechanism of β-eudesmol in human dermal fibroblast has not been reported yet, and also, there have been no researches on β-eudesmol as skin care and cosmetic compounds.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and ECM gene expression modulations of β-eudesmol via NF-κB signaling pathway in normal human dermal fibroblasts

Kim¹

2018

biomed dermatol

View full text Add to dashboard Cite

Background: β-eudesmol is a kind of aromatic compound belonging to sesquiterpenoid which exists within not only the bark of magnolia but also Nardostachys jatamansi, Atractylodes lancea, Pterocarpus santalinus, Ginkgo bilobal, Cryptomeria japonica, etc., and there has been progress in medical and pharmaceutic researches on antitumor, anticancer, and anti-inflammatory effects; nervous system stabilization; and vasodilator effects, etc., but not in researches on skin cares and cosmetics at all. Therefore, this study pretreated β-eudesmol with human dermal fibroblasts (HDFs) and then gave oxidative stresses with H 2 O 2 to examine antioxidation, anti-inflammatory, and cell preservation effects. Through this process, it proves the possibility of β-eudesmol as cosmetic materials. Methods: This study verified the effectiveness of β-eudesmol through cell viability analysis, reactive oxygen estimation, associated β-galactosidase assay, nuclear factor-kappa B (NF-κB) luciferase assay, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: The cell viability which decreased due to H 2 O 2 increased as per dose-dependent manners of β-eudesmol. Also, at the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay, intracellular reactive oxygen species (ROS) quantitative analysis and glutathione (GSH) estimation, the relative levels which were changed by H 2 O 2 treatment, showed attenuated or protective transition forms, depending on the concentration of β-eudesmol. Additionally, reduced superoxide dismutase 1 (SOD1) and catalase (CAT) gene expression by H 2 O 2 were increased by β-eudesmol. As the result of the promoter activity analysis of NF-κB which has a key role in inflammation and skin aging, NF-κB activity decreases as β-eudesmol concentration increases, and also this study proves that gene expression of interleukin 1 beta (IL-1β) which is a downstream gene of NF-κB related to inflammatory response decreases as well as tumor necrosis factor-alpha (TNF-α) gene expression depending on the concentration of β-eudesmol. Conclusions: Through these results, this study suggests there are anti-inflammatory effects by shutting out the NF-κB pathway. Following the results of the extracellular matrix (ECM) regulating gene expression analysis, this study proves that oxidative stress-induced increased MMP1 levels were decreased depending on the concentration of β-eudesmol and verifies that it hinders the collapse of collagen through inhibition of transcriptional activity of NF-κB. From the result of β-eudesmol regulating tissue inhibitors of metalloproteinase (TIMP)-1 gene expression which hinders matrix metalloproteinase (MMP), activation and alteration of gene expression of collagen type I alpha 1 (COL1A1) underpins the above consequences. Through this research, it is considered that β-eudesmol as one of natural cosmetic materials with such effects as antioxidation, anti-inflammation, and cell preservation is worthy of notice.

show abstract

“…β-eudesmol could significantly promote the gastrointestinal motility in mice (Wang et al, 2002). It has been demonstrated to be an inhibitor for tumor growth (Ma et al, 2008). It might also aid the development of drugs to treat angiogenic diseases (Tsuneki et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Identification and quantification of sesquiterpenes and polyacetylenes in Atractylodes lancea from various geographical origins using GC-MS analysis

Ouyang¹,

Zhang²,

Zhao³

et al. 2012

Rev. bras. farmacogn.

View full text Add to dashboard Cite

A convenient and sensitive GC-MS method was developed to identify thirteen sesquiterpenes and polyacetylenes (e.g. caryophyllene, γ-elemene, α-caryophyllene, β-selinene, isoledene, germacrene B, elixene, atractylone, hinesol, β-eudesmol, atrctylodin, atractylenolide II and acetylatractylodinol) in Atractylodes lancea (Thunb.) DC., Asteraceae. Among those compounds, four major components including atractylone, hinesol, β-eudesmol and atrctylodin were quantified with standards; contents of other components were estimated by using calibration curve of hinesol. In this study, we presented that the concentrations of those thirteen components varied drastically in A. lancea samples from different producing areas. Among those components, atractylenolide II and acetylatractylodinol were identified by GC-MS for the first time. A hierarchical clustering analysis based on relative peak areas of those thirteen components in total ion current (TIC) profiles was used to characterize A. lancea samples from different producing areas. Further clustering analysis showed that a simplified method with only four major bioactive components could be used to serve the same aim.

show abstract

β-Eudesmol suppresses tumour growth through inhibition of tumour neovascularisation and tumour cell proliferation

Cited by 56 publications

References 14 publications

Eudesmol Isomers Induce Caspase‐Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

Eudesmol Isomers Induce Caspase‐Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

Anti-inflammatory and ECM gene expression modulations of β-eudesmol via NF-κB signaling pathway in normal human dermal fibroblasts

Identification and quantification of sesquiterpenes and polyacetylenes in Atractylodes lancea from various geographical origins using GC-MS analysis

Contact Info

Product

Resources

About