Cytotoxic and NF-κB inhibitory sesquiterpene lactones from Piptocoma rufescens

Ren, Yulin; Acuña, Ulyana Muñoz; Jiménez, Francisco; Garcia, Ricardo Alexandrino; Mejía, Melciades; Chai, Heebyung; Gallucci, Judith C.; Farnsworth, Norman R.; Soejarto, Djaja D.; Blanco, Esperanza J. Carcache de; Kinghorn, A. Douglas

doi:10.1016/j.tet.2012.01.061

Cited by 39 publications

(81 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As part of a drug discovery program, GZL was previously identified as a potent NF-κB inhibitor on HeLa cervical cancer cells when using an Elisa assay ( Ren et al ., 2012 ). The NF-κB inhibition (IC 50 = 3.8 μM) was compared to the effects exhibited by rocaglamide (IC 50 = 0.075 μM), a potent inhibitor of the NF-κB signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

“…This compound was first isolated from Eremanthus goyazensis as part of a research program to find schistosomicidal agents( Vichnewski et al ., 1976 ), and was obtained subsequently from Eremanthus mattogrossensis ( Lunardello et al ., 1995 ), Lychnophora granmongolense (Grael et al . 2000), Lychnophora pohlii ( Grael et al ., 2005a ), Camchaya calcarea ( Vongvanich et al ., 2006 ), Centratherum punctatum ( Valdes et al ., 1998 ), and Piptocoma rufescens ( Ren et al ., 2012 ). GZL, isolated previously from Piptocoma rufescens in our research program, exhibits multiple bioactivities, including schistosomicidal, trypanocidal ( Grael et al ., 2005b ; Vichnewski et al ., 1976 ; Grael et al ., 2005a Borkosky et al ., 2009 ), antimycobacterial ( Vongvanich et al ., 2006 ), cytotoxic ( Dos Santos et al ., 2004 ; Vongvanich et al ., 2006 ; Ren et al ., 2012) and genotoxic (Mantovani et al ., 1993) effects.…”

Section: Introductionmentioning

confidence: 99%

“…2000), Lychnophora pohlii ( Grael et al ., 2005a ), Camchaya calcarea ( Vongvanich et al ., 2006 ), Centratherum punctatum ( Valdes et al ., 1998 ), and Piptocoma rufescens ( Ren et al ., 2012 ). GZL, isolated previously from Piptocoma rufescens in our research program, exhibits multiple bioactivities, including schistosomicidal, trypanocidal ( Grael et al ., 2005b ; Vichnewski et al ., 1976 ; Grael et al ., 2005a Borkosky et al ., 2009 ), antimycobacterial ( Vongvanich et al ., 2006 ), cytotoxic ( Dos Santos et al ., 2004 ; Vongvanich et al ., 2006 ; Ren et al ., 2012) and genotoxic (Mantovani et al ., 1993) effects. It has also been reported by our research group that this compound shows nuclear factor kappa B (NF-κB) inhibitory activity ( Rungeler et al ., 1999 ; Siedle et al ., 2004 ; Wagner et al ., 2006 ; Ren et al ., 2012 ).…”

Section: Introductionmentioning

confidence: 99%

“…As part of a search for new anticancer agents from diverse organisms ( Kinghorn et al ., 2009 ), GZL showed both cytotoxic and NF-κB p65 inhibitory activities in vitro ( Ren et al ., 2012 ). In the present study, the antitumor efficacy of GZL was evaluated using a mice model.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Goyazensolide Induces Apoptosis in Cancer Cells in vitro and in vivo

Acuña¹,

Shen²,

Ren³

et al. 2013

International J. of Cancer Research

Self Cite

View full text Add to dashboard Cite

As part of the screening program for anticancer agents from natural sources, the sesquiterpene lactone goyazensolide (GZL) was identified as a potent NF-κB inhibitor. The hollow-fiber assay was used to evaluate the anti-tumor efficacy of GZL in vivo. The mechanistic effects of GZL were evaluated in the HT-29 colonic cell line to reveal the pathway through which GZL exerts its effects. NF-κB subunits p65 and p50 were inhibited, and the upstream mediator IκB kinase (IKKβ) was downregulated in a dose-dependent manner. Apoptosis was mediated by caspase-3, and cell cycle arrest was detected in G1-phase. Consequently, 96% of the cell population was in sub G1-phase after treatment with GZL (10 μM).The antitumor effect of GZL was observed at a dose of 12.5 mg/kg. Cell adhesion was affected as a result of NF-κB inhibition. GZL appears to selectively target the transcription factor NF-κB. In summary, GZL sensitizes HT-29 colon cancer cells to apoptosis and cell death in a dose-dependent manner both in vivo and in vitro, through NF-κB inhibition (IC50 = 3.8 μM). Thus, it is a new potent lead compound for further development into a new effective chemotherapeutic agent.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Goyazensolide Induces Apoptosis in Cancer Cells in vitro and in vivo

Acuña¹,

Shen²,

Ren³

et al. 2013

International J. of Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the treatment options available for estrogenindependent tumors are far from satisfactory. In recent years, the search for new antitumor substances obtained from plants or their synthetic analogs has been a hot research activity (2)(3)(4).…”

mentioning

confidence: 99%

Proteomic Analysis of Proteins Engaged in α‐Methylene‐δ‐Lactone Cytotoxic Effects in Hormone‐Independent Breast Cancer MDA‐MB‐231 Cells

et al. 2014

View full text Add to dashboard Cite

A simple synthetic α-methylene-δ-lactone, 1-isopropyl-2-methylene-1,2-dihydrobenzochromen-3-one, designated DL-3, was shown previously to induce apoptosis and significantly suppress cell metastatic potential in MDA-MB-231 breast cancer cells. The mechanisms through which DL-3 exerts its effects are poorly understood. The purpose of this study was to investigate the protein expression profiles in MDA-MB-231 cells exposed to the DL-3 treatment. Using 2D differential gel electrophoresis, a set of eight differentially expressed proteins (spot intensities which showed ≥1.25-fold change and statistical significance, p < 0.05, between the control and DL-3-treated group) were found and successfully identified by mass spectrometry (MALDI-TOF/MS). The proteomic results revealed that the presence of DL-3 in MDA-MB-231 cells led to the differential regulation of some proteins that are involved in the cell cycle progression, apoptosis, cytokinesis, modulation of transcription, cellular signaling, and vesicular trafficking. The function of other identified proteins is still unknown. Therefore, our data indicate new directions for the further studies of the pathways engaged in the anticancer action exerted by α-methylene-δ-lactones in cancer cells.

show abstract

Validation of analytical procedures using HPLC‐ELSD to determine six sesquiterpene lactones in Eremanthus species

Sousa

Nogueira

Ferreira

et al. 2015

Biomedical Chromatography

View full text Add to dashboard Cite

Eremanthus species display sesquiterpene lactones with therapeutic potential. We are proposing the development of a new analytical method that has been completely validated to qualify Eremanthus species and its main lactones in raw material using HPLC-ELSD. For the sample preparation, 10.0 mg of powdered Eremanthus leaves was extracted with a 5 mL MeOH/H2 O (9:1 v/v) solution containing scopoletin at 140 µg/mL as the internal standard. For the separation of eight compounds, six of which were lactones, one internal (IS) and one secondary standard were performed utilizing monolithic columns with a nonlinear gradient. The selectivity, stability, precision and matrix effects parameters showed values of RSD of <10%. The six lactones and scopoletin (IS) were recovered with a proportion between 74 and 90% with accuracy represented by error at -25.41%. The linear dynamic range was obtained between 10.0 and 310.0 µg/mL for all compounds with r(2) > 0.9987. The limits of detection and quantitation ranged from 2.00 to 6.79 µg/mL and from 6.00 to 20.40 µg/mL, respectively. Assessing the robustness study, this method can be used in inter-laboratory studies. Using the HPLC-ELSD method, six sesquiterpene lactones including 4β,5-dihydro-2',3'-dihydroxy-15-deoxy-goyazensolide, goyazensolide, 4β,5-dihydro-2',3'-epoxy-15-deoxy-goyazensolide, centratherin, 4β,5-dihydro-15-deoxy-goyazensolide and lychnofolide, were detected and quantified from distinct Eremanthus species, which were collected in different regions.

show abstract

Cytotoxic and NF-κB inhibitory sesquiterpene lactones from Piptocoma rufescens

Cited by 39 publications

References 40 publications

Goyazensolide Induces Apoptosis in Cancer Cells in vitro and in vivo

Goyazensolide Induces Apoptosis in Cancer Cells in vitro and in vivo

Proteomic Analysis of Proteins Engaged in α‐Methylene‐δ‐Lactone Cytotoxic Effects in Hormone‐Independent Breast Cancer MDA‐MB‐231 Cells

Validation of analytical procedures using HPLC‐ELSD to determine six sesquiterpene lactones in Eremanthus species

Contact Info

Product

Resources

About