Induction of apoptosis in HT-29 cells by quercetin through mitochondria-mediated apoptotic pathway

Li, Zhaohui; Gao, Qiang

doi:10.1080/19768354.2013.793210

Cited by 13 publications

(12 citation statements)

References 18 publications

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“…Briefly, cells were stained with 5 µl Annexin V-FITC and 5 µl PI in each sample. After incubation for 15 min at room temperature in the dark, the degree of apoptosis was quantified as a percentage of the Annexin V-positive and PI-negative cells by flow cytometry (21).…”

Section: Assessment Of Apoptosis By Flow Cytometrymentioning

confidence: 99%

Momilactone B induces apoptosis and G1 arrest of the cell cycle in human monocytic leukemia U937 cells through downregulation of pRB phosphorylation and induction of the cyclin-dependent kinase inhibitor p21Waf1/Cip1

Park¹,

Jeong²,

Kim³

et al. 2014

Oncology Reports

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Abstract. Momilactone B, a terpenoid phytoalexin present in rice bran, has been shown to exhibit several biological activities. The present study was conducted using cultured human leukemia U937 cells to elucidate the possible mechanisms by which momilactone B exerts its anticancer activity, which to date has remained poorly understood. Momilactone B treatment of U937 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by chromatin condensation, DNA fragmentation, the cleavage of poly(ADP-ribose) polymerase and Annexin V-FITC staining. Flow cytometric analysis revealed that momilactone B resulted in G1 arrest in cell cycle progression, which was associated with the dephosphorylation of retinoblastoma protein (pRB) and enhanced binding of pRB with the E2F transcription factor family proteins. Treatment with momilactone B also increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21Waf1/Cip1 in a p53-independent manner, without any noticeable changes in G1 cyclins and cyclin-dependent kinases (Cdks), except a slight decrease in cyclin E. Moreover, in vitro kinase assay indicated that momilactone B significantly decreased Cdk4-and Cdk6-associated kinase activities through a notably increased binding of p21 to Cdk4 and Cdk6. Our results demonstrated that momilactone B caused G1 cell cycle arrest and apoptosis in U937 cells through the induction of p21 expression, inhibition of Cdk/cyclin-associated kinase activities, and reduced phosphorylation of pRB, which may be related to anticancer activity. IntroductionImpaired deregulated cell cycle progression and induction of apoptosis are the primary characteristics of cancer cells due to an imbalance between proliferation and cell death. In terms of cell cycle regulation, the cyclin-dependent kinases (Cdks) are the key regulators of eukaryotic cell cycle progression in cooperation with various endogenous cyclins and Cdks (1,2). An alteration in the cooperation may lead to increased or decreased cell growth and proliferation followed by differentiation and/or cell death by apoptosis (3,4). Therefore, the key regulators of cell cycle progression and apoptotic induction may be important molecular targets for therapeutic intervention, and inhibition of cell cycle regulation may be particularly useful in the treatment of diseases caused by uncontrolled cell proliferation, such as cancer.In general, passage through G1 into the S phase is regulated by the activities of D-type cyclin-and cyclin E-associated Cdks. D-type cyclins bind to existing Cdk4 and Cdk6, forming active complexes. The complexes in turn phosphorylate the retinoblastoma susceptibility protein (pRB). The hyperphosphorylated pRB dissociates from the E2F/DP1/pRB Momilactone B induces apoptosis and G1 arrest of the cell cycle in human monocytic leukemia U937 cells through downregulation of pRB phosphorylation and induction of the cyclin-dependent kinase inhibitor p21Waf1/Cip1

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Section: Assessment Of Apoptosis By Flow Cytometrymentioning

confidence: 99%

Momilactone B induces apoptosis and G1 arrest of the cell cycle in human monocytic leukemia U937 cells through downregulation of pRB phosphorylation and induction of the cyclin-dependent kinase inhibitor p21Waf1/Cip1

Park¹,

Jeong²,

Kim³

et al. 2014

Oncology Reports

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“…Results are expressed as fold increase of the activity measured in samples. Fold‐increase activity can be determined by comparing the results of treated samples with the level of the uninduced control .…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Tolmetin Hydrazide–Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells

Küçükgüzel

Koç

Çıkla-Süzgün

et al. 2015

Archiv der Pharmazie

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Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, (1)H NMR) methods. N'-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76 μM against colon cancer line HT-29 (ATCC, HTB-38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site.

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“…The cells were stained with annexin V-FITC and PI in each sample. After incubation for 15 min at room temperature in the dark, the degree of apoptosis was quantified as a percentage of the annexin V-positive and PI-negative (annexin V + /PI – cells) cells by a flow cytometer ( Li and Gao, 2013 ).…”

Section: Methodsmentioning

confidence: 99%

The Histone Deacetylase Inhibitor Trichostatin A Sensitizes Human Renal Carcinoma Cells to TRAIL-Induced Apoptosis through Down-Regulation of c-FLIPL

Han

Park

Kwon

et al. 2015

Biomolecules & Therapeutics

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Histone acetylation plays a critical role in the regulation of transcription by altering the structure of chromatin, and it may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating the gene expression of components of the TRAIL signaling pathway. In this study, we investigated the effects and molecular mechanisms of trichostatin A (TSA), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in Caki human renal carcinoma cells. Our results indicate that nontoxic concentrations of TSA substantially enhance TRAIL-induced apoptosis compared with treatment with either agent alone. Cotreatment with TSA and TRAIL effectively induced cleavage of Bid and loss of mitochondrial membrane potential (MMP), which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase (PARP), contributing toward the sensitization to TRAIL. Combined treatment with TSA and TRAIL significantly reduced the levels of the cellular Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (c-FLIP), whereas those of death receptor (DR) 4, DR5, and FADD remained unchanged. The synergistic effect of TAS and TRAIL was perfectly attenuated in c-FLIPL-overexpressing Caki cells. Taken together, the present study demonstrates that down-regulation of c-FLIP contributes to TSA-facilitated TRAIL-induced apoptosis, amplifying the death receptor, as well as mitochondria-mediated apoptotic signaling pathways.

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Induction of apoptosis in HT-29 cells by quercetin through mitochondria-mediated apoptotic pathway

Cited by 13 publications

References 18 publications

Momilactone B induces apoptosis and G1 arrest of the cell cycle in human monocytic leukemia U937 cells through downregulation of pRB phosphorylation and induction of the cyclin-dependent kinase inhibitor p21Waf1/Cip1

Momilactone B induces apoptosis and G1 arrest of the cell cycle in human monocytic leukemia U937 cells through downregulation of pRB phosphorylation and induction of the cyclin-dependent kinase inhibitor p21Waf1/Cip1

Synthesis of Tolmetin Hydrazide–Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells

The Histone Deacetylase Inhibitor Trichostatin A Sensitizes Human Renal Carcinoma Cells to TRAIL-Induced Apoptosis through Down-Regulation of c-FLIPL

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