Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells

Ka, Hyeon; Park, Hee-Juhn; Jung, Hyun‐Ju; Choi, Jin-Keun; Cho, Kyu-Seok; Ha, Joohun; Lee, Kyung‐Tae

doi:10.1016/s0304-3835(03)00238-6

Cited by 311 publications

(205 citation statements)

References 25 publications

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“…At concentrations of CIN higher than used in our study, other researchers found that CIN depleted intracellular glutathione and protein thiol levels and increased reactive oxygen species (ROS) levels in mammalian cells [36,37]. Increased levels of ROS in turn induced apoptosis via decreased mitochondrial transmembrane potential and release of cytochrome c [37]. In the present study, increased transcription of the glutathione synthesis genes GCLM and GCLC is suggestive of glutathione depletion after CIN treatment.…”

Section: Discussionsupporting

confidence: 60%

“…Results from previous studies in bacterial strains, have suggested that VAN and CIN reduce spontaneous and induced mutagensis by similar mechanisms, principally through enhancement of recombinational repair. However, results from the present study, along with recently published studies in mammalian cells [30,[35][36][37], suggest that VAN and CIN may enhance recombinational repair through different mechanisms, possibly by inducing different types of DNA damage. Based on observations of the requirement for recA gene function in E. coli for the antimutagenic and survival-enhancing effects of VAN and CIN [7,8,10], Ohta et al [10] hypothesized that these antimutagens may inhibit mutations induced by chemical mutagens (e.g., 4-nitroquinoline) or physical mutagens (e.g., UV-light) by enhancing recombinational repair.…”

Section: Discussionsupporting

confidence: 47%

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Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair

King

Shaughnessy

Mure

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Vanillin (VAN) and cinnamaldehyde (CIN) are dietary flavorings that exhibit antimutagenic activity against mutagen-induced and spontaneous mutations in bacteria. Although these compounds were antimutagenic against chromosomal mutations in mammalian cells, they have not been studied for antimutagenesis against spontaneous gene mutations in mammalian cells. Thus, we initiated studies with VAN and CIN in human mismatch repair-deficient (hMLH1 − ) HCT116 colon cancer cells, which exhibit high spontaneous mutation rates (mutations/cell/generation) at the HPRT locus, permitting analysis of antimutagenic effects of agents against spontaneous mutation. Long-term (1-3-week) treatments of HCT116 cells with VAN at minimally toxic concentrations (0.5-2.5 mM) reduced the spontaneous HPRT mutant fraction (MF, mutants/10 6 survivors) in a concentrationrelated manner by 19% to 73%. A similar treatment with CIN at 2.5-7.5 μM yielded a 13% to 56% reduction of the spontaneous MF. Short-term (4-h) treatments also reduced the spontaneous MF by 64% (VAN) and 31% (CIN). To investigate the mechanisms of antimutagenesis, we evaluated the ability of VAN and CIN to induce DNA damage (comet assay) and to alter global gene expression (Affymetrix GeneChip) after 4-h treatments. Both VAN and CIN induced DNA damage in both mismatch repair-proficient (HCT116 + chr3) and deficient (HCT116) cells at concentrations that were antimutagenic in HCT116 cells. There were 64 genes in common whose expression was changed similarly by both VAN and CIN; these included genes related to DNA damage, stress responses, oxidative damage, apoptosis, and cell growth. RT-PCR results paralleled the Affymetrix results for 4 selected genes (HMOX1, DDIT4, GCLM, and CLK4). Our results show for the first time that VAN and CIN Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. These and other data lead us to propose that VAN and CIN may induce DNA damage that elicits recombinational DNA repair and, consequently, reduces spontaneous mutation. NIH Public Access

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 47%

Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair

King

Shaughnessy

Mure

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…With the exception of being a skin irritant, TCA has low toxicity. Recent documented data showed TCA could induce the apoptosis of several human tumor cell lines, including human promyelocytic leukemia HL-60 cells [3,4] . Interestingly, TCA has been shown to interfere with T cell activation through different mechanisms and could, therefore, have additive effects on the inhibition of T cell activation [5] .…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells

Zhang

Liu²,

et al. 2010

Acta Pharmacol Sin

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“…1). Cinnamaldehyde, a major component of cinnamon tree, has been known to induce intracellular ROS generation, leading to apoptotic cell death 21,22 . Cinnamaldehyde contains active Michael acceptor pharmacophore and is given the Generally Recognized as Safe status with approval for use in food in the United States 22 .…”

mentioning

confidence: 99%

“…Cinnamaldehyde contains active Michael acceptor pharmacophore and is given the Generally Recognized as Safe status with approval for use in food in the United States 22 . Cinnamaldehyde has been reported to induce ROS generation mainly in the mitochondria and inhibit growth of human cancer cells, but minimal cytotoxicity to normal cells 21,23,24 . However, the clinical applications of cinnamaldehyde have been limited by its poor bioavailability (a short half-life in blood) due to rapid oxidation of aldehyde group and lower drug efficacy than common anticancer drugs 21,25,26 .…”

mentioning

confidence: 99%

Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death

et al. 2015

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Cancer cells, compared with normal cells, are under oxidative stress associated with the increased generation of reactive oxygen species (ROS) including H 2 O 2 and are also susceptible to further ROS insults. Cancer cells adapt to oxidative stress by upregulating antioxidant systems such as glutathione to counteract the damaging effects of ROS. Therefore, the elevation of oxidative stress preferentially in cancer cells by depleting glutathione or generating ROS is a logical therapeutic strategy for the development of anticancer drugs. Here we report a dual stimuli-responsive hybrid anticancer drug QCA, which can be activated by H 2 O 2 and acidic pH to release glutathione-scavenging quinone methide and ROS-generating cinnamaldehyde, respectively, in cancer cells. Quinone methide and cinnamaldehyde act in a synergistic manner to amplify oxidative stress, leading to preferential killing of cancer cells in vitro and in vivo. We therefore anticipate that QCA has promising potential as an anticancer therapeutic agent.

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Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells

Cited by 311 publications

References 25 publications

Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair

Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair

Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells

Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death

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