Effect of Combination Treatments of Apigenin and Chemotherapy on Apoptosis- Related Genes and Proteins in Acute Leukaemia Cell Lines

Abstract Apigenin is a dietary polyphenol found abundantly in fruit and vegetables. It has been shown to sensitize acute lymphoid and myeloid leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and alkylating agents (e.g., cyclophosphamide), reducing ATP levels and inducing apoptosis; whilst being protective to control haematopoietic stem cells. This study analysed the expression profiles of intrinsic and extrinsic apoptosis-related genes and proteins to help elucidate the mechanisms of action of apigenin when used in combination with etoposide or cyclophosphamide in acute lymphoid and myeloid leukaemia cells (Jurkat and THP-1). Expression of apoptosis-related genes were measured using a TaqMan® Human Apoptosis Array and the StepOne Plus RT-qPCR System, whilst apoptosis-related proteins were determined using a protein profilerTM-human apoptosis array and the LI-COR OdysseyR Infrared Imaging System. Apigenin when combined with etoposide or cyclophosphamide-induced apoptosis via the mitochondrial pathway, increasing the expression of pro-apoptotic cytochrome c, SMAC/DIABLO, and HTRA2/OMI, which promoted caspase-9 and -3 activation. Targeting anti-apoptotic and/or pro-apoptotic members of the apoptotic pathways is a promising strategy to induce cancer cell death and improve sensitivity to chemotherapy agents.Here apigenin in combination with etoposide or cyclophosphamide induced apoptosis in leukaemia cells and may have clinical potential in the treatment of leukaemia.

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Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa

The Journal of Cell Biology ◽

10.1083/jcb.200608070 ◽

2007 ◽

Vol 176 (4) ◽

pp. 415-424 ◽

Cited By ~ 75

Author(s):

Edwina Naik ◽

Ewa M. Michalak ◽

Andreas Villunger ◽

Jerry M. Adams ◽

Andreas Strasser

Keyword(s):

Ultraviolet Radiation ◽

Dominant Role ◽

Death Receptor ◽

Mouse Skin ◽

Mitochondrial Pathway ◽

Minor Role ◽

Apoptotic Pathway ◽

Apoptotic Pathways ◽

Induced Apoptosis ◽

A Minor

To identify the mechanisms of ultraviolet radiation (UVR)–induced cell death, for which the tumor suppressor p53 is essential, we have analyzed mouse embryonic fibroblasts (MEFs) and keratinocytes in mouse skin that have specific apoptotic pathways blocked genetically. Blocking the death receptor pathway provided no protection to MEFs, whereas UVR-induced apoptosis was potently inhibited by Bcl-2 overexpression, implicating the mitochondrial pathway. Indeed, Bcl-2 overexpression boosted cell survival more than p53 loss, revealing a p53-independent pathway controlled by the Bcl-2 family. Analysis of primary MEFs lacking individual members of its BH3-only subfamily identified major initiating roles for the p53 targets Noxa and Puma. In the transformed derivatives, where Puma, unexpectedly, was not induced by UVR, Noxa had the dominant role and Bim a minor role. Furthermore, loss of Noxa suppressed the formation of apoptotic keratinocytes in the skin of UV-irradiated mice. Collectively, these results demonstrate that UVR activates the Bcl-2–regulated apoptotic pathway predominantly through activation of Noxa and, depending on cellular context, Puma.

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Farnesol-Induced Apoptosis in Candida albicans

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01551-08 ◽

2009 ◽

Vol 53 (6) ◽

pp. 2392-2401 ◽

Cited By ~ 151

Author(s):

Mark E. Shirtliff ◽

Bastiaan P. Krom ◽

Roelien A. M. Meijering ◽

Brian M. Peters ◽

Jingsong Zhu ◽

...

Keyword(s):

Candida Albicans ◽

Protein Expression ◽

Mammalian Cells ◽

Expression Profiles ◽

Fluorescent Microscopy ◽

Physiological Role ◽

Fungal Cell ◽

Apoptotic Pathways ◽

Induced Apoptosis ◽

Protein Expression Profiles

ABSTRACT Farnesol, a precursor in the isoprenoid/sterol pathway, was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. Farnesol is involved in the inhibition of germination and biofilm formation by C. albicans and can be cytotoxic at certain concentrations. In addition, we have shown that farnesol can trigger apoptosis in mammalian cells via the classical apoptotic pathways. In order to elucidate the mechanism behind farnesol cytotoxicity in C. albicans, the response to farnesol was investigated, using proteomic analysis. Global protein expression profiles demonstrated significant changes in protein expression resulting from farnesol exposure. Among the downregulated proteins were those involved in metabolism, glycolysis, protein synthesis, and mitochondrial electron transport and the respiratory chain, whereas proteins involved in folding, protection against environmental and oxidative stress, actin cytoskeleton reorganization, and apoptosis were upregulated. Cellular changes that accompany apoptosis (regulated cell death) were further analyzed using fluorescent microscopy and gene expression analysis. The results indicated reactive oxygen species accumulation, mitochondrial degradation, and positive terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) in the farnesol-exposed cells concurrent with increased expression of antioxidant-encoding and drug response genes. More importantly, the results demonstrated farnesol-induced upregulation of the caspase gene MCA1 and the intracellular presence of activated caspases. In conclusion, this study demonstrated that farnesol promotes apoptosis in C. albicans through caspase activation, implying an important physiological role for farnesol in the fungal cell life cycle with important implications for adaptation and survival.

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Transforming Growth Factor-β1 Induces Apoptosis through Fas Ligand-independent Activation of the Fas Death Pathway in Human Gastric SNU-620 Carcinoma Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e03-04-0201 ◽

2004 ◽

Vol 15 (2) ◽

pp. 420-434 ◽

Cited By ~ 65

Author(s):

Sang Gyun Kim ◽

Hyun-Soon Jong ◽

Tae-You Kim ◽

Jung Weon Lee ◽

Noe Kyeong Kim ◽

...

Keyword(s):

Fas Ligand ◽

Transforming Growth Factor ◽

Death Receptor ◽

Transforming Growth Factor Β1 ◽

Mitochondrial Pathway ◽

Carcinoma Cells ◽

Caspase 8 ◽

Apoptotic Pathways ◽

Induced Apoptosis ◽

Tgf Β1

To date, two major apoptotic pathways, the death receptor and the mitochondrial pathway, have been well documented in mammalian cells. However, the involvement of these two apoptotic pathways, particularly the death receptor pathway, in transforming growth factor-β1 (TGF-β1)-induced apoptosis is not well understood. Herein, we report that apoptosis of human gastric SNU-620 carcinoma cells induced by TGF-β1 is caused by the Fas death pathway in a Fas ligand-independent manner, and that the Fas death pathway activated by TGF-β1 is linked to the mitochondrial apoptotic pathway via Bid mediation. We showed that TGF-β1 induced the expression and activation of Fas and the subsequent caspase-8-mediated Bid cleavage. Interestingly, expression of dominant negative FADD and treatment with caspase-8 inhibitor efficiently prevented TGF-β1-induced apoptosis, whereas the treatment with an activating CH11 or a neutralizing ZB4 anti-Fas antibody, recombinant Fas ligand, or Fas-Fc chimera did not affect activation of Fas and the subsequent induction of apoptosis by TGF-β1. We further demonstrated that TGF-β1 also activates the mitochondrial pathway showing Bid-mediated loss of mitochondrial membrane potential and subsequent cytochrome c release associated with the activations of caspase-9 and the effector caspases. Moreover, all these apoptotic events induced by TGF-β1 were found to be effectively inhibited by Smad3 knockdown and also completely abrogated by Smad7 expression, suggesting the involvement of the Smad3 pathway upstream of the Fas death pathway by TGF-β1.

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Involvement of G2/M Cell Cycle Arrest and the Mitochondrial Pathway in Boletopsis leucomelaena (Pers.) Fayod (Agaricomycetideae) Lectin-Induced Apoptosis of Human Leukemia U937 Cells

International Journal of Medicinal Mushrooms ◽

10.1615/intjmedmushr.v7.i12.190 ◽

2005 ◽

Vol 7 (1-2) ◽

pp. 201-212 ◽

Cited By ~ 3

Author(s):

Yu Koyama ◽

Takuji Suzuki ◽

Akane Kajiya ◽

Mamoru Isemura

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Mitochondrial Pathway ◽

Human Leukemia ◽

U937 Cells ◽

M Cell ◽

Cycle Arrest ◽

Induced Apoptosis

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Evaluation of Validity of the Near-infrared Imaging System (VistaCam iX Proxi) in Comparison With Digital Radiographic Findings and ICDAS-II in Detection of Approximal Carious Lesions: Diagnostic Accuracy Study.

Case Medical Research ◽

10.31525/ct1-nct03923192 ◽

2019 ◽

Author(s):

Keyword(s):

Diagnostic Accuracy ◽

Near Infrared ◽

Infrared Imaging ◽

Imaging System ◽

Diagnostic Accuracy Study ◽

Radiographic Findings ◽

Infrared Imaging System ◽

Carious Lesions ◽

Icdas Ii ◽

Accuracy Study

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Lamotrigine Attenuates Proteasome Inhibition-Induced Apoptosis by Suppressing the Activation of the Mitochondrial Pathway and the Caspase-8- and Bid-Dependent Pathways

Neurochemical Research ◽

10.1007/s11064-016-1962-5 ◽

2016 ◽

Vol 41 (10) ◽

pp. 2503-2516 ◽

Cited By ~ 4

Author(s):

Yoon Jeong Nam ◽

Arum Kim ◽

Min Sung Lee ◽

Yong Kyoo Shin ◽

Dong Suep Sohn ◽

...

Keyword(s):

Proteasome Inhibition ◽

Mitochondrial Pathway ◽

Caspase 8 ◽

Induced Apoptosis

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Stachyose-induced apoptosis of Caco-2 cells via the caspase-dependent mitochondrial pathway

Food & Function ◽

10.1039/c4fo01017e ◽

2015 ◽

Vol 6 (3) ◽

pp. 765-771 ◽

Cited By ~ 15

Author(s):

Guidong Huang ◽

Jian Mao ◽

Zhongwei Ji ◽

Aisikaer Ailati

Keyword(s):

Colon Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Mitochondrial Pathway ◽

Colon Cancer Cell ◽

Cancer Cell Growth ◽

Induced Apoptosis

Some studies have shown that stachyose, as prebiotics, can prevent indirectly colon cancer cell growth by promoting the proliferation of probiotics or producing beneficial materials in the intestine.

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