Flavone inhibition of tumor growth via apoptosis in vitro and in vivo

Chen, Yen-Chou; Shen, Shing‐Chuan; Chow, Julie Chi; Ko, Ching Huai; Tseng, Shih Wen

doi:10.3892/ijo.25.3.661

Cited by 48 publications

(52 citation statements)

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“…The incidence of cancer increases when Asian women move to the United States, where the average diet is rich in fat and confers a strong significant protective effect during adolescence. Flavonoids and flavone exert a broad spectrum of biological effects by targeting genes involved in regulation of tumor cell proliferation, the cell cycle, and apoptosis, thus reducing the risk of cancer or inhibiting the growth of tumor cells [16,24,25,26,27]. Such effects were apparent in the present study.…”

Section: Discussionmentioning

confidence: 52%

“…We next examined the effect of flavone on expression of p21Waf1, an inhibitor of cell cycle progression, given that flavone-induced inhibition of the growth of colon tumor cells in vitro and in vivo is associated with both the induction of apoptosis and up-regulation of p21 Waf1 gene expression [16]. Furthermore, p21Waf1 is thought to be a downstream target of DLC-2, a member of the DLC family closely related to DLC-1 [20].…”

Section: Resultsmentioning

confidence: 99%

“…Based on previous results with protein and mRNA profiling and other studies, in all experiments the concentration of 15μM flavone (2-phenyl-4H-1-benzopyran-4-one; Sigma, St. Louis, MO) was used [12,16]. For cell proliferation assay, cells were seeded in triplicate in 96-well plates (1 × 10 4 cells per well) and cultured with flavone for up to 4 days.…”

Section: Assay Of Cell Proliferationmentioning

confidence: 99%

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Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Ullmannova

Popescu

2007

Cancer Detection and Prevention

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Background-Dietary flavone was previously shown to increase the expression of deleted in liver cancer-1 gene (DLC-1) in HT-29 colon carcinoma cell line (Proteomics 2004;4:2455-64). DLC-1 that encodes a Rho GTPase-activating protein, functions as a tumor suppressor gene and is frequently inactivated or down-regulated in several common cancers. Restoration of DLC-1 expression suppresses in vitro tumor cells proliferation and tumorigenicity in vivo.Methods-Here, the effect of flavone was examined in several DLC-1-deficient cell lines derived from different types human cancer using assays for cell proliferation, gene expression and transfer.Results-We show that exposure to 15μM flavone increased DLC1 expression in breast but not in liver or prostate carcinoma cells or a nonmalignant breast epithelial cell line. Flavone restored the expression of DLC1 in the breast carcinoma cell lines MDA-MB-468, MDA-MB-361, and BT20 as well as in the colon carcinoma cell line HT-29 all of which are DLC-1-negative due to promoter hypermethylation. We further show that flavone inhibited cell proliferation, induced cell cycle arrest at G2-M, increased p21 Waf1 gene expression, and caused apoptosis. Microarray analysis of these aggressive and metastatic breast carcinoma cells revealed 29 flavone-responsive genes, among which the DNA damage-inducible GADD genes were up-regulated and the proto-oncogene STMN1 and IGFBP3 were down-regulated.Conclusions-Flavone-mediated alterations of genes that regulate tumor cell proliferation, cell cycle, and apoptosis contribute to chemopreventive and antitumoral effects of flavone. Alone or in combination with demethylating agents, flavone may be an effective adjunct to chemotherapy in preventing breast cancer metastasis.

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Section: Discussionmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Assay Of Cell Proliferationmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Ullmannova

Popescu

2007

Cancer Detection and Prevention

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“…Over the years, numerous activities have been assigned to this flavone. Morin has been shown to inhibit the growth of COLO205 cells in nude mice (1), exhibit intestinal anti-inflammatory activity in the acute phase of the trinitrobenzenesulfonic acid model of rat colitis (2,3), inhibit azoxymethane-induced aberrant crypt foci in rats (4), exhibit chemopreventive effects on chemically induced rat tongue carcinogenesis (5), and exert anti-inflammatory effects and reduce the incidence of lipopolysaccharide (LPS) -induced septic shock (6). Morin has also been shown to suppress phorbol ester -induced transformation of hepatocytes (7).…”

mentioning

confidence: 99%

“…How morin mediates these effects is not fully understood. Morin has been shown to induce p21 and activate caspases (1), suppress AKT activation and induce stress kinase activation (8), abolish peroxisome proliferator-activated receptor activity (11), inhibit P-glycoprotein (12), inhibit lipooxygenase-1 (13), suppress inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression in macrophages (14), and inhibit the release of inflammatory cytokines, such as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF) from mast cells (15).…”

mentioning

confidence: 99%

Morin (3,5,7,2′,4′-Pentahydroxyflavone) Abolishes Nuclear Factor-κB Activation Induced by Various Carcinogens and Inflammatory Stimuli, Leading to Suppression of Nuclear Factor-κB–Regulated Gene Expression and Up-regulation of Apoptosis

Manna

Aggarwal

Sethi

et al. 2007

Clinical Cancer Research

121

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Purpose: Morin is a flavone that exhibits antiproliferative, antitumor, and anti-inflammatory effects through a mechanism that is not well understood. Because of the role of transcription factor nuclear factor-nB (NF-nB) in the control of cell survival, proliferation, tumorigenesis, and inflammation, we postulated that morin mediates its effects by modulating NF-nB activation. Experimental Design: We investigated the effect of morin on NF-nB pathway activated by inflammatory agents, carcinogens, and tumor promoters. The effect of this flavone on expression of NF-nB^regulated gene products involved in cell survival, proliferation, and invasion was also examined. Results: We showed by DNA-binding assay that NF-nB activation induced by tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate, lipopolysaccharide, ceramide, interleukin-1, and H 2 O 2 was suppressed by morin; the suppression was not cell type specific. The suppression of NF-nB by morin was mediated through inhibition of InBa (inhibitory subunit of NF-nB) kinase, leading to suppression of phosphorylation and degradation of InBa and consequent p65 nuclear translocation. Morin also inhibited the NF-nB^dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR1-associated death domain, TNFR-associated factor 2, NFnB^inducing kinase, InB kinase, and the p65 subunit of NF-nB. NF-nB^regulated gene products involved in cell survival [inhibitor of apoptosis (IAP) 1, IAP2, X chromosome-linked IAP, Bcl-xL, and survivin], proliferation (cyclin D1and cyclooxygenase-2), and invasion (matrix metalloproteinase-9) were down-regulated by morin. These effects correlated with enhancement of apoptosis induced byTNF and chemotherapeutic agents. Conclusion: Overall, our results indicate that morin suppresses the activation of NF-nB and NF-nB^regulated gene expression, leading to enhancement of apoptosis. This may provide the molecular basis for the ability of morin to act as an anticancer and anti-inflammatory agent.

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Characterization of cells with different mitochondrial membrane potential during apoptosis

et al. 2005

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During Qu-induced apoptosis, loss of DeltaPsi, PS exposure, and decrease of mitochondrial mass are early events that precede permeability to PI and loss of DNA. Populations of cells with different DeltaPsi, as revealed by flow cytometry after JC-1 staining, differed also for other parameters associated to apoptosis. Thus, the simultaneous analysis of several parameters by polychromatic flow cytometry permits a better identification of many stages of cell death, and, more in general, allows to evaluate the eventual heterogenic sensibility of the population under study to a given compound.

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Flavone inhibition of tumor growth via apoptosis in vitro and in vivo

Cited by 48 publications

References 0 publications

Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Morin (3,5,7,2′,4′-Pentahydroxyflavone) Abolishes Nuclear Factor-κB Activation Induced by Various Carcinogens and Inflammatory Stimuli, Leading to Suppression of Nuclear Factor-κB–Regulated Gene Expression and Up-regulation of Apoptosis

Characterization of cells with different mitochondrial membrane potential during apoptosis

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