Inhibition of IAP’s and activation of p53 leads to caspase-dependent apoptosis in gastric cancer cells treated with Scutellarein

Saralamma, Venu Venkatarame Gowda; Lee, Ho Jeong; Raha, Suchismita; Lee, Won Sup; Kim, Eun Hee; Lee, Sang Joon; Heo, Jeong‐Doo; Won, Chung-Kil; Kang, Chang Keun; Kim, Gon Sup

doi:10.18632/oncotarget.23202

Cited by 29 publications

(20 citation statements)

References 40 publications

(43 reference statements)

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“…Apoptosis is accompanied with a reduction of the G1 phase cells and an increase in the G2/M phase cells, signifying a cell cycle arrest in G2/M phase. Moreover, similar results were observed with previous studies showing that an increase in the number of G2/M phase cells is clearly related to apoptosis [ 31 , 32 ]. In the current study, we found that PEC treatment decreased the percentage of G1 phase and increased sub-G1 and G2/M phase cells.…”

Section: Discussionsupporting

confidence: 92%

Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway

et al. 2018

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Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.

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Section: Discussionsupporting

confidence: 92%

Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway

et al. 2018

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“…The Bcl/Bax ratio is considered an important determinant of the apoptosis induction [14] and in this study, we found that chrysophanol increased Bax expression and decreased the Bcl-2 expression, thereby causing a remarkable decrease in the Bcl-2/Bax ratio. Apoptosis is also accompanied by the activation of the caspases [15] and in this study, we found that chrysophanol induced the activation of caspase-3 and 9 in a dose-dependent pattern. These observations are also supported by previous studies where chrysophanol has been shown to trigger apoptosis of the breast cancer cells [16].…”

Section: Discussionsupporting

confidence: 68%

Antitumor Effects of Chrysophanol in Malignant Optic Nerve Meningioma Cell Lines are Mediated via Caspase Activation, Induction of Mitochondrial Mediated Apoptosis, Mitochondrial Membrane Depolarization and Targeting the Mitogen-Activated Protein Kinase Signaling Pathway

Zeng¹,

Guo²,

Chen³

et al. 2019

Pharmacology

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Background: Anthroquinones are considered remarkable anticancer agents. Chrysophanol is an important anthroquinone and it has shown to have the potential to inhibit the growth of the range of cancers. However, there are no studies regarding the anticancer effects of chrysophanol against the malignant meningioma of optic nerve. In this review, the potential of chrysophanol in the treatment of malignant meningioma of optic nerve was explored by evaluating its anticancer activity against the malignant meningioma CH157-MN cells. Materials and Methods: The 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay was used for cell viability determination. The 4′,6-diamidino-2-phenylindole (DAPI), acridine orange and ethidium bromide (AO/EB) and annexin V/PI assays were used to determine the induction of apoptosis. The potential of reactive oxygen species and the mitochondrial membrane was estimated by flow cytometry. Western blot analysis was performed to determine the protein expression. Results: The results showed that chrysophanol caused significant decline in the viability of the CH157-MN cells and exhibited an IC50 of 30 µmol/L. Anticancer effects were found to be due to the induction of apoptosis as evident form the DAPI and AO/EB staining. The annexin V/PI staining revealed that the apoptotic cells increased from 1.77% in control to 37.21% at 60 µmol/L concentration of chrysophanol. The Bcl-2/Bax expression ratio was decreased and the caspases-3 and 9 were activated upon chrysophanol treatment of the CH157-MN cells. Chrysophanol also triggered the formation of reactive oxygen species and reduction of the mitochondrial membrane potential in the CH157-MN cells and also blocked the Mitogen-activated protein kinase signaling pathway. Conclusion: The findings of the present study suggest that chrysophanol may prove beneficial in the treatment of malignant meningioma of optic nerve. Key Message: The study revealed the anticancer potential of chrysophanol against the malignant optic nerve meningioma.

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“…These findings support the hypothesis that different mechanisms may be responsible for the efficacy of JQ1 in NETs, and these may involve the apoptotic pathway, as indicated by our RNA-Seq analysis that revealed four apoptosis-associated genes (Capn9, Dffb, Birc3 and Nfkb1) to be downregulated by JQ1 treatment. Birc3 encodes cIAP2, which is an E3 ubiquitin protein ligase that is a member of the inhibitors of apoptosis proteins (IAP) family, and increases cIAP2 expression that can lead to evasion of caspase-mediated apoptosis in different cancers including gastric and gallbladder cancers and glioblastoma (Wang et al 2016, Jiang et al 2017, Gowda Saralamma et al 2018. In addition, cIAP2 has been reported to activate NFκB (encoded by Nfkb1) signalling, which also has roles in apoptosis regulation (Tchoghandjian et al 2013, Jiang et al 2017.…”

Section: Discussionmentioning

confidence: 99%

Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells

Lines

Filippakopoulos

Stevenson

et al. 2020

Endocrine-Related Cancer

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Medical treatments for corticotrophinomas are limited, and we therefore investigated the effects of epigenetic modulators, a new class of anti-tumour drugs, on the murine adrenocorticotropic hormone (ACTH)-secreting corticotrophinoma cell line AtT20. We found that AtT20 cells express members of the bromo and extra-terminal (BET) protein family, which bind acetylated histones, and therefore, studied the anti-proliferative and pro-apoptotic effects of two BET inhibitors, referred to as (+)-JQ1 (JQ1) and PFI-1, using CellTiter Blue and Caspase Glo assays, respectively. JQ1 and PFI-1 significantly decreased proliferation by 95% (P < 0.0005) and 43% (P < 0.0005), respectively, but only JQ1 significantly increased apoptosis by >50-fold (P < 0.0005), when compared to untreated control cells. The anti-proliferative effects of JQ1 and PFI-1 remained for 96 h after removal of the respective compound. JQ1, but not PFI-1, affected the cell cycle, as assessed by propidium iodide staining and flow cytometry, and resulted in a higher number of AtT20 cells in the sub G1 phase. RNA-sequence analysis, which was confirmed by qRT-PCR and Western blot analyses, revealed that JQ1 treatment significantly altered expression of genes involved in apoptosis, such as NFκB, and the somatostatin receptor 2 (SSTR2) anti-proliferative signalling pathway, including SSTR2. JQ1 treatment also significantly reduced transcription and protein expression of the ACTH precursor pro-opiomelanocortin (POMC) and ACTH secretion by AtT20 cells. Thus, JQ1 treatment has anti-proliferative and pro-apoptotic effects on AtT20 cells and reduces ACTH secretion, thereby indicating that BET inhibition may provide a novel approach for treatment of corticotrophinomas.

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Inhibition of IAP’s and activation of p53 leads to caspase-dependent apoptosis in gastric cancer cells treated with Scutellarein

Cited by 29 publications

References 40 publications

Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway

Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric Cancer Cell via PI3K/AKT/mTOR Signaling Pathway

Antitumor Effects of Chrysophanol in Malignant Optic Nerve Meningioma Cell Lines are Mediated via Caspase Activation, Induction of Mitochondrial Mediated Apoptosis, Mitochondrial Membrane Depolarization and Targeting the Mitogen-Activated Protein Kinase Signaling Pathway

Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells

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