Apoptosis-inducing natural products found in utero during murine pregnancy

Liberles, Stephen D.; Schreiber, Stuart L.

doi:10.1016/s1074-5521(00)00114-9

Cited by 10 publications

(8 citation statements)

References 21 publications

(32 reference statements)

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“…Apoptosis is a fundamental, energy-dependent biological mechanism [31,39], which can be triggered by a diverse array of stimuli, including phytochemicals [40,41]. The reduction of ΔΨm by Maldi 531.2[M + H] + in the present study strongly indicates initiation of apoptotic events and inhibition of cell proliferation by dissipation of the mitochondrial membrane potential.…”

Section: Discussionmentioning

confidence: 55%

A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells

Dapat

Jacinto

Efferth

2013

BMC Complement Altern Med

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BackgroundBioactivity-guided fractionation of extracts of Aglaia loheri Blanco (Meliaceae) yielded a cytotoxic isolate, termed Maldi 531.2[M + H]+. This phenolic ester was further investigated for its in vitro cytotoxicity toward human CCRF-CEM leukemia cells and their multi-drug resistant (MDR) subline, CEM/ADR5000. The intrinsic mitochondrial membrane potential (ΔΨm) and induction of apoptosis by this isolate were evaluated.MethodsChromatography techniques, mass spectrometry and proton NMR were employed to isolate Maldi 531.2[M + H]+. XTT cell proliferation and viability assay was used for cytotoxic test, and JC-1[5’,5’,6,6’,-tetrachloro-1,1’,3,3’-tetraethylbenzimidazoyl carbocyanine iodide was used to assess ΔΨm and initiation of apoptosis; Annexin V/FITC-PI staining was employed to analyse apoptosis.ResultsMaldi 531.2[M + H]+ was cytotoxic towards both CCRF-CEM and CEM/ADR5000 cells with IC50 values of 0.02 and 0.03 μM, respectively. The mitochondrial membrane potential (ΔΨm) of MDR cells was significantly reduced in a dose-dependent manner leading to apoptosis as detected by flow cytometric Annexin V-FITC/ PI staining.ConclusionMaldi 531.2[M + H]+ may be a potential anti-cancer drug candidate whose mode of action include reduction of the mitochondrial membrane potential and induction of apoptosis.

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Section: Discussionmentioning

confidence: 55%

A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells

Dapat

Jacinto

Efferth

2013

BMC Complement Altern Med

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“…11 Therefore, it is not surprising that activation of lipoxygenases has been associated to programmed death of different cells and tissues, induced by different, unrelated stimuli (Table 1 and references therein). Several studies have shown the proapoptotic activity of 5-LOX, 15,23 of leukocyte type 12-LOX, 21,26 and of 15-LOX, 24,28 and have indicated molecular targets for lipoxygenase interaction able to contribute to the induction of apoptosis (Table 2 and references therein).…”

Section: Lipoxygenase Involvement In Apoptotic Pathwaysmentioning

confidence: 99%

Lipoxygenases and their involvement in programmed cell death

2001

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Lipoxygenases are a family of enzymes which dioxygenate unsaturated fatty acids, thus initiating lipoperoxidation of membranes and the synthesis of signaling molecules. Consequently, they induce structural and metabolic changes in the cell in a number of pathophysiological conditions. Recently, a pro-apoptotic effect of lipoxygenase, and of the hydroperoxides produced thereof, has been reported in different cells and tissues, leading to cell death. Anti-apoptotic effects of lipoxygenases have also been reported; however, this has often been based on the use of enzyme inhibitors. Here we review the characteristics of the lipoxygenase family and its involvement in the initiation of oxidative stress-induced apoptosis. Finally, we discuss the role of lipoxygenase activation in apoptosis of animal and plant cells, suggesting a common signal transduction pathway in cell death conserved through evolution of both kingdoms. Cell Death and Differentiation (2001) 8, 776 ± 784.

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“…Other advantages associated with rats are their easy availability, large litter sizes, ease of handling, high fertility rate, short gestation period, low spontaneous malformation rate, genetic stability and lack of seasonal breeding. Various biocomponents, such as creatine, lactate, glutamate, glutamine, alanine, aspartate, aspargine, taurine, fatty acid and choline, have been reported to have pivotal roles during embryonal growth and development, [40][41][42][43][44][45][46][47][48][49][50] and variation in any of them may cause an ailment in the developing embryos and foetuses. 36 It is also teratogenic in various laboratory animal species, 25,37,38 as well as Table 3 Anomalies and malformations observed among the embryos of dams from various groups treated with a vehicle control or various doses of cyclophosphamide (CP) a in humans, 39 and the teratogenicity of which can be characterized by stunted growth, and central nervous system, facial, and skeletal anomalies.…”

Section: Discussionmentioning

confidence: 99%

A novel approach for testing the teratogenic potential of chemicals on the platform of metabolomics: studies employing HR-MAS nuclear magnetic resonance spectroscopy

et al. 2015

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NMR based metabolomics offers a complementary approach that gives information on whole-organism functional integrity over time after drug exposure. Hence the objective was to develop a quick, reliable method for testing the teratogenic potential of a new chemical entity (NCE) on the platform of metabonomics, as an alternative to conventional procedures. Time mated Charles Foster rats (n ¼ 9)were injected with cyclophosphamide (0, 5, 15 and 30 mg kg À1 ) at different dose levels on day 11 of the pregnancy, through an i.p. route. On day 12 of the pregnancy, embryos were procured from six rats out of the 9 pregnant rats from each group, using a per abdominal approach. These embryos were then undertaken for morphological studies and NMR experiments using a high resolution-magic angle spin (HR-MAS) probe. The remaining three rats were followed until term to procure full term pups, which were used for conventional observations and studies. Multivariate unsupervised principal component analysis of the 1 H NMR spectra from the rat embryos revealed a dose dependent cluster separation between the controls and treated specimens, which was further confirmed by supervised partial leastsquares discriminant analysis with an R 2 of 0.77 and Q 2 of 0.72. Those embryos which were found to have malformations/anomalies, significantly presented a few upregulated (aspartate) and a few downregulated (creatine, choline and glycine) metabolite levels. This work revealed that observed teratogenic ailments and resulting metabolic profiles have a definite correlation, demonstrating the suitability of this procedure for testing teratogenicity, which may give a new dimension to the prioritization of lists having a large number of chemicals to be tested for their teratogenicity.Malformations observed among the full term pups also validated the findings from the embryos.

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Apoptosis-inducing natural products found in utero during murine pregnancy

Cited by 10 publications

References 21 publications

A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells

A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells

Lipoxygenases and their involvement in programmed cell death

A novel approach for testing the teratogenic potential of chemicals on the platform of metabolomics: studies employing HR-MAS nuclear magnetic resonance spectroscopy

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