Upregulation of Death Receptor 5 and Production of Reactive Oxygen Species Mediate Sensitization of PC-3 Prostate Cancer Cells to TRAIL Induced Apoptosis by Vitisin A

Shin, Deokil; Kwon, Hee Young; Sohn, Eun Jung; Nam, Moon Sik; Kim, Jung Hyo; Lee, Jae Chul; Ryu, Shi‐Yong; Park, Byungchun; Kim, Sung‐Hoon

doi:10.1159/000430286

Cited by 25 publications

(10 citation statements)

References 43 publications

(37 reference statements)

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“…Furthermore, TNF receptors may be involved in ROS and ERK pathway and they may play a role as the agent-triggers of molecular signaling in the cells stimulated with securinine. During activation of cellular TNF receptors, oxidative stress may increase [32, 33] and lead to the cell cycle arrest that was observed in our study.…”

Section: Discussionmentioning

confidence: 59%

Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells

et al. 2016

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BackgroundThe Securinega-type alkaloids occur in plants belonging to Euphorbiaceae family. One of the most widely distributed alkaloid of this group is securinine, which was identified next to allosecurinine in Phyllanthus glaucus (leafflower). Recently, some Securinega-type alkaloids have paid attention to its antiproliferative potency towards different cancer cells. However, the cytotoxic properties of allosecurinine have not yet been evaluated.MethodsThe cytotoxicity of the extract, alkaloid fraction obtained from P. glaucus, isolated securinine and allosecurinine against HeLa cells was evaluated by real-time xCELLigence system and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and 7-amino-actinomycin (7-AAD) staining and confirmed with fluorescent Hoechst 33342 dye. The assessment of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, the level of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), caspase-3/7 activity and cell cycle analysis were measured by flow cytometry. The enzymatic activity of caspase-9 was assessed by a luminometric assay. The expression of apoptosis associated genes was analyzed by real-time PCR.ResultsThe experimental data revealed that securinine and the alkaloid fraction were significantly potent on HeLa cells growth inhibition with IC50 values of 7.02 ± 0.52 μg/ml (32.3 μM) and 25.46 ± 1.79 μg/ml, respectively. The activity of allosecurinine and Phyllanthus extract were much lower. Furthermore, our study showed that the most active securinine induced apoptosis in a dose-dependent manner in the tested cells, increased the percentage of ROS positive cells and depolarized cells as well as stimulated the activity of ERK1/2, caspase-9 and -3/7. Securinine also induced cell cycle arrest in S phase. Real-time PCR analysis showed high expression of TNFRSF genes in the cells stimulated with securinine.ConclusionsSecurinine induces apoptosis and activates cell cycle checkpoints in HeLa cells which is associated with oxidative stress. The results indicate that the mitochondrial pathway is involved in the programmed cell death.

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Section: Discussionmentioning

confidence: 59%

Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells

et al. 2016

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“…TRAIL binds DR4 and DR5 to activate FADD (Fas‐associating protein with a novel death domain), which induces activation of several proapoptotic and antiapoptotic proteins . As shown in Figure A, the expression levels of cleaved caspase‐3 and caspase‐8 was significantly increased in cells after treated with Periplocin and TRAIL, suggesting that combined treatment with Periplocin and TRAIL induced more gastric cancer cell apoptosis through the mitochondrial apoptosis pathway than treatment with TRAIL or Periplocin alone.…”

Section: Resultsmentioning

confidence: 93%

Antitumor Effect of Periplocin in TRAIL‐Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2‐EGR1 pathway

Zhao

Huang³

et al. 2019

Molecular Carcinogenesis

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Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), a member of the tumor necrosis factor family, induces apoptosis in a variety of cancer cells. However, gastric cancer (GC) cells are insensitive to TRAIL usually. In the previous study, we showed that Periplocin could induce apoptosis in GC cells via the activation of ERK1/2‐EGR1 pathway. In the present study, we have shown that the combination of Periplocin and TRAIL had a greater inhibitory effect on gastric cancer cell viability in vitro and in vivo than Periplocin or TRAIL alone. Through upregulating the expression of DR4 and DR5 at transcriptional and protein levels, Periplocin enhanced the sensitivity of gastric cancer cells to TRAIL. Furthermore, enhanced activity of ERK1/2‐EGR1 pathway was responsible for upregulating of DR4 and DR5 uponPeriplocin treatment, subsequently reducing the expression of Mcl‐1 and Bcl2 and activating Bid and caspase‐3/8. Collectively, these data implied that Periplocin might act as a sensitizer of TRAIL and could be a potential strategy for the treatment of GC.

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“…Shin et al [46] demonstrate that the TNFRSF10C/DcR1 as well as TNFRSF10A/DR4 and TNFRSF10B/ DR5 participate in apoptotic and antioxidant effects of vitisin A, derived from wine grapes, the underlying antitumor mechanism in prostate cancer cells. Upregulation of TNFRSF10B/DR5 and production of reactive oxygen species mediate sensitization of PC-3 prostate cancer cells to TRAIL induced apoptosis by vitisin A [47]. Combined treatment of PC-3 cells with vitisin A and TRAIL increased the production of reactive oxygen species, DR5 promoter activity, its cell surface expression, and enhanced cytotoxicity.…”

Section: Tumor Necrosis Factor-related Decoy Receptorsmentioning

confidence: 97%

The role of the TNF receptors and apoptosis inducing ligands in tumor growth

Minchenko¹,

Tsymbal²,

Minchenko³

et al. 2016

Ukr.Biochem.J.

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Tumor necrosis factor (TNF) superfamily receptors and TNF apoptosis inducing ligands play an important role in the realization of TNF function and control tumor growth. The TNF-related pathways are controlled by endoplasmic reticulum stress signaling, which has a crucial role in the control of cell proliferation and tumor growth. Furthermore, the inhibition of IRE1 (inositol requiring enzyme-1), which is a central mediator of endoplasmic reticulum stress sand mainly responsible for cell proliferation and apoptosis, leads to suppression of tumor growth through specific changes in the expression of genes encoding transcription factors, tumor suppressors, angiogenesis and apoptosis related proteins, including TNF superfamily receptors and TNF apoptosis inducing ligands. Therefore, changes in the expression level of TNF-related genes encoding TNF superfamily receptors and apoptosis inducing ligands possibly reflect metabolic reprogramming of cancer cells upon inhibition of IRE1-mediated endoplasmic reticulum stress signaling and correlate with suppression of glioma cell proliferation.

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Upregulation of Death Receptor 5 and Production of Reactive Oxygen Species Mediate Sensitization of PC-3 Prostate Cancer Cells to TRAIL Induced Apoptosis by Vitisin A

Cited by 25 publications

References 43 publications

Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells

Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells

Antitumor Effect of Periplocin in TRAIL‐Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2‐EGR1 pathway

The role of the TNF receptors and apoptosis inducing ligands in tumor growth

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