Liriodenine enhances the apoptosis effect of valproic acid in human colon cancer cells through oxidative stress upregulation and Akt inhibition

Chen, Chung‐Yi; Li, Zih‐Ling; Chung, King‐Thom; Lu, Fung‐Jou; Chen, Ching‐Hsein

doi:10.1016/j.procbio.2014.07.022

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…The aporphine alkaloids anonaine, glaucine, and norglaucine were previously reported as inductors of oxidative stress [ 18 ]. In addition, liriodenine/valproic acid combination treatment enhances ROS production and intracellular GSH depletion [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Xylopine Induces Oxidative Stress and Causes G₂/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells

Santos

Silva

Menezes

et al. 2017

Oxidative Medicine and Cellular Longevity

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Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells. Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-α), reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway. Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells. Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells.

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Section: Discussionmentioning

confidence: 99%

Xylopine Induces Oxidative Stress and Causes G₂/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells

Santos

Silva

Menezes

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…In the present study, animals received this dose for 7 days. These toxic effects are associated with oxidative stress as a result of the disruption of the balance between oxidant and antioxidant systems (Chang and Abbott 2006;Yis et al 2009;Chateauvieux et al 2010;Kiang et al 2010;Sokmen et al 2012;Chen et al 2014). VPA toxicity has been shown to increase ROS formation.…”

Section: Discussionmentioning

confidence: 99%

Effects of Chard (Beta Vulgaris L. Var. Cicla) on Cardiac Damage in Valproic Acid-Induced Toxicity

Üstündağ

Tunalı

Alev

et al. 2015

Journal of Food Biochemistry

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The aim of this study was to examine the effects of chard on valproic acid (VPA)-induced cardiac damage. Female Sprague-Dawley rats were grouped as control, chard given control (100 mg/kg/day, by gavage), VPA (500 mg/kg/day, intraperitoneally) and chard given VPA (100 mg/kg/day chard by gavage, 500 mg/kg/day VPA, intraperitoneally). The aqueous extracts of chard leaves were given 1 h prior to administration of VPA for 7 days. Malondialdehyde (MDA), total sialic acid (SA) levels and catalase (CAT) activity significantly increased in the VPA group compared with the control group (P < 0.05). Chard administration significantly decreased MDA and SA levels in the control and in the VPA groups (P < 0.05). Chard administration also significantly increased CAT activities and glutathione levels both in the control and in the VPA groups (P < 0.05). As a conclusion, chard consumption may prevent cardiac tissue from oxidative stress and inflammation in VPA-induced toxicity.

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“…The analyses of DNA damage and the cell cycle were performed by staining with PI and flow cytometry, as previously described (17,18). The cells (1x10 6 ) were cultured in 60 mm tissue culture dishes at 37˚C for 24 h. The RPMI 1640 culture medium (Hyclone; GE Healthcare Life Sciences, Logan, UT, USA) was replaced with fresh medium, and the cells were exposed to 0.60, 0.75 and 1.50x10 -3 % of the yellow pigment and 5.0, 12.5 and 25.0x10 -3 % of the green pigment at 37˚C for 48 h. Subsequently, the cells were pooled, washed with phosphate-buffered saline (PBS), fixed in a PBS-methanol (volume/volume, 1:2) solution at room temperature for 5 min and then incubated at 4˚C for at least 18 h. Following washing with PBS once, the cell pellets were stained with the PI solution supplemented with PBS, 40 µg/ml PI and 40 µg/ml of DNase-free RNase A (Sigma-Aldrich; Merck KGaA) for 30 min at room temperature in the dark and then analyzed using a Becton-Dickinson FACScan flow cytometer (BD Biosciences, Franklin Lakes, NJ, USA).…”

Section: Analysis Of Seed Oil Pigments From C Inophyllum Lmentioning

confidence: 99%

Yellow and green pigments from Calophyllumï¿½inophyllum L. seed oil induce cell death in colon and lung cancer cells

et al. 2018

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Abstract. Natural compounds have been candidates for anticancer medicine over the last 20 years. During the process of isolating seed oil from Calophyllum inophyllum L., yellow and green pigments containing multiple compounds with an aromatic structure were identified. High-performance liquid chromatography and nuclear magnetic resonance analysis of these pigments revealed that the compounds present were identical, but the concentration of the compounds was different. Treatment with the pigments was able to induce the death of DLD-1 human colon cancer cells and increase the percentage of the cells in the sub-G 1 and sub-G 2 /M phases in a dose-dependent manner. Additionally, the pigments were able to exhibit cytotoxic activity on A549 and H1975 human non-small cell lung cancer (NSCLC) cell lines at 24 h, with half-maximal inhibitory concentrations (IC 50 ) values of 0.1206 and 0.0676%, respectively for green pigments, and 0.0434 and 0.0501%, respectively for yellow pigments. Furthermore, a decrease in IC 50 value was associated with an increase in the duration of treatment. However, a sharp decrease in IC 50 value of the yellow pigment was observed for H1975 cells at 48 h and for A549 cells at 72 h compared with no change in IC 50 value for the green pigment with time, suggesting that the pigments function and induce cell death differently in the two cell lines. An investigation was performed into the synergistic effect of the green pigment and gefitinib (Iressa ® , ZD1839), which is a selective epidermal growth factor receptor-tyrosine kinase inhibitor to block growth factor-mediated cell proliferation. The combination of the green pigment and gefitinib resulted in an enhancement of the decrease in viability of A549 and H1975 cells compared with treatment with gefitinib alone, which suggested that treatment with the green pigments was able to enhance the sensitivity of NSCLC cells to gefitinib. In conclusion, these pigments may be considered for development as anti-colon cancer agents.

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Liriodenine enhances the apoptosis effect of valproic acid in human colon cancer cells through oxidative stress upregulation and Akt inhibition

Cited by 5 publications

References 34 publications

Xylopine Induces Oxidative Stress and Causes G₂/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells

Xylopine Induces Oxidative Stress and Causes G₂/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells

Effects of Chard (Beta Vulgaris L. Var. Cicla) on Cardiac Damage in Valproic Acid-Induced Toxicity

Yellow and green pigments from Calophyllumï¿½inophyllum L. seed oil induce cell death in colon and lung cancer cells

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Liriodenine enhances the apoptosis effect of valproic acid in human colon cancer cells through oxidative stress upregulation and Akt inhibition

Cited by 5 publications

References 34 publications

Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells

Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells

Effects of Chard (Beta Vulgaris L. Var. Cicla) on Cardiac Damage in Valproic Acid-Induced Toxicity

Yellow and green pigments from Calophyllumï¿½inophyllum L. seed oil induce cell death in colon and lung cancer cells

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Xylopine Induces Oxidative Stress and Causes G₂/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells

Xylopine Induces Oxidative Stress and Causes G₂/M Phase Arrest, Triggering Caspase‐Mediated Apoptosis by p53‐Independent Pathway in HCT116 Cells