Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells

Kuo, Shiu‐Ming

doi:10.1016/s0304-3835(96)04458-8

Cited by 293 publications

(140 citation statements)

References 23 publications

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“…As far as we know, there are no studies on effects of procyanidins on adipose differentiation. Although most studies of the antiproliferative effects of flavonoids have been carried out in cancerous cells, [46][47][48][49] there is also evidence that proliferation is inhibited by flavonoids in 3T3-L1. Genistein, a soy flavonoid, was shown to inhibit both proliferation and differentiation in 3T3-L1 when added at the induction of differentiation, 6 and this induced growth arrest was accompanied by an increase in p21 expression and subsequent cyclin E/CDK 2 supression.…”

Section: Discussionmentioning

confidence: 99%

Grape-seed derived procyanidins interfere with adipogenesis of 3T3-L1 cells at the onset of differentiation

et al. 2005

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OBJECTIVE: Our group's previous results on the effects of a grape seed procyanidin extract (GSPE) on adipose metabolism showed that peroxisome proliferator-activated receptor-g (PPARg) plays a central role in the lipolytic effects of GSPE on adipocytes. Since PPARg2 is a main regulator of the differentiation process of adipocytes, we investigated whether GSPE affects the adipogenesis of 3T3-L1 cells. DESIGN: We performed a time point screening by treating 3T3-L1 cells with GSPE during the differentiation process for 24 h. MEASUREMENTS: Differentiation markers and differential gene expression due to GSPE treatment (using the microarray technique). RESULTS: Twenty four hour-GSPE treatment at the onset of differentiation reduces adipose-specific markers and maintains the expression of preadipocyte marker preadipocyte factor-1 (Pref-1) significantly elevated. These effects were not found in other time points. Microarray analysis of gene expression after GSPE treatment at the early stage of differentiation showed a modified gene expression profile in which cell cycle and growth-related genes were downregulated by GSPE. CONCLUSION: These results suggest that GSPE affects adipogenesis, mainly at the induction of differentiation, and that procyanidins may have a new role in which they impede the formation of adipose cells.

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Section: Discussionmentioning

confidence: 99%

Grape-seed derived procyanidins interfere with adipogenesis of 3T3-L1 cells at the onset of differentiation

et al. 2005

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“…Furthermore, recent evidence has shown that quercetin is extensively metabolized to O-methylated and glucuronide metabolites during absorption in the small intestine and in the liver (17,18), and such metabolites should be taken into consideration to provide in vivo relevance for any mechanism. Quercetin itself has been thoroughly investigated for its abilities to express anti-proliferative effects (19,20) and induce death predominantly by an apoptotic mechanism in cancer cell lines (21)(22)(23). For example, it has been observed to induce caspase-3 activation in the malignant cell line HPB-ALL (24), activate caspase-3 and caspase-9, release cytochrome c in HL-60 cells (25), and induce chromatin and nuclear fragmentation in colonic cancer cells (20).…”

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confidence: 99%

“…Quercetin itself has been thoroughly investigated for its abilities to express anti-proliferative effects (19,20) and induce death predominantly by an apoptotic mechanism in cancer cell lines (21)(22)(23). For example, it has been observed to induce caspase-3 activation in the malignant cell line HPB-ALL (24), activate caspase-3 and caspase-9, release cytochrome c in HL-60 cells (25), and induce chromatin and nuclear fragmentation in colonic cancer cells (20). On the other hand, quercetin treatment has been shown to suppress the c-Jun N-terminal kinase (JNK) 1 activity and apoptosis induced by hydrogen peroxide (26) and 4-hydroxy-2-nonenal (27).…”

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Modulation of Pro-survival Akt/Protein Kinase B and ERK1/2 Signaling Cascades by Quercetin and Its in Vivo Metabolites Underlie Their Action on Neuronal Viability

Spencer

Rice‐Evans

Williams

2003

Journal of Biological Chemistry

312

224

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Much recent interest has focused on the potential of flavonoids to interact with intracellular signaling pathways such as with the mitogen-activated protein kinase cascade. We have investigated whether the observed strong neurotoxic potential of quercetin in primary cortical neurons may occur via specific and sensitive interactions within neuronal mitogen-activated protein kinase and Akt/protein kinase B (PKB) signaling cascades, both implicated in neuronal apoptosis. Quercetin induced potent inhibition of both Akt/PKB and ERK phosphorylation, resulting in reduced phosphorylation of BAD and a strong activation of caspase-3. High quercetin concentrations (30 M) led to sustained loss of Akt phosphorylation and subsequent Akt cleavage by caspase-3, whereas at lower concentrations (<10 M) the inhibition of Akt phosphorylation was transient and eventually returned to basal levels. Lower levels of quercetin also induced strong activation of the pro-survival transcription factor cAMP-responsive element-binding protein, although this did not prevent neuronal damage. O-Methylated quercetin metabolites inhibited Akt/PKB to lesser extent and did not induce such strong activation of caspase-3, which was reflected in the lower amount of damage they inflicted on neurons. In contrast, neither quercetin nor its O-methylated metabolites had any measurable effect on c-Jun N-terminal kinase phosphorylation. The glucuronide of quercetin was not toxic and did not evoke any alterations in neuronal signaling, probably reflecting its inability to enter neurons. Together these data suggest that quercetin and to a lesser extent its O-methylated metabolites may induce neuronal death via a mechanism involving an inhibition of neuronal survival signaling through the inhibition of both Akt/PKB and ERK rather than by an activation of the c-Jun N-terminal kinase-mediated death pathway.

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“…Genistein in particular possesses several anti-tumorigenic activities in vitro, including inhibition of angiogenesis (Fotsis et al, 1993), topoisomerase (Okura et al, 1988) and tyrosine kinase (Ogawara et al, 1989) activity, in addition to having antioxidant properties (Wei et al, 1993). Experiments using colon cancer cell lines have shown that genistein, and the related isoflavone biochanin A, can inhibit cell proliferation and induce apoptosis (Yanagihara et al, 1993;Kuo, 1996), again implying protective effects.No data are available to demonstrate the effects of isoflavones on normal intestinal cell lines. In this study we aimed to investigate the proliferative and apoptotic effects of genistein in vitro on normal intestinal epithelial cells and compare these to the effects on malignant cell lines.…”

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Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro

et al. 1999

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The incidence of intestinal cancer is high in Western populations but is relatively uncommon in Asia and Africa (Boyle et al, 1985). It is thought that this variation in incidence is strongly influenced by diet (Armstrong and Doll, 1975;Adlercreutz, 1990) and it is estimated that about 32% of deaths by all cancers, and 70% of deaths from colorectal cancer, could be prevented by a change in diet (Willet, 1995). There is also evidence to suggest that a high intake of soya-based foods (as in populations of Southeast Asia) could contribute to a reduced incidence of mammary (Lee et al, 1995) and prostate (Severson et al 1989) cancer.Soya beans are an abundant source of the isoflavones genistein, daidzein and glyceitin (Wang and Murphy, 1994). These diphenol molecules are structurally similar to the steroidal oestrogens and thus, have been termed phyto-oestrogens. Due to this similarity, attention has focused on the role of phyto-oestrogens in preventing both hormonally mediated (particularly breast) and hormonally independent cancers. Soya metabolites may reduce the risk of colon cancers (Messina et al, 1994). Genistein in particular possesses several anti-tumorigenic activities in vitro, including inhibition of angiogenesis (Fotsis et al, 1993), topoisomerase (Okura et al, 1988) and tyrosine kinase (Ogawara et al, 1989) activity, in addition to having antioxidant properties (Wei et al, 1993). Experiments using colon cancer cell lines have shown that genistein, and the related isoflavone biochanin A, can inhibit cell proliferation and induce apoptosis (Yanagihara et al, 1993;Kuo, 1996), again implying protective effects.No data are available to demonstrate the effects of isoflavones on normal intestinal cell lines. In this study we aimed to investigate the proliferative and apoptotic effects of genistein in vitro on normal intestinal epithelial cells and compare these to the effects on malignant cell lines. We also aimed to examine the effects of some novel isoflavones, which have been synthesized primarily as specific tyrosine kinase inhibitors, upon the same cell lines. The effects of these isoflavones are compared with the effects of oestradiol, the anti-oestrogen tamoxifen, and the specific tyrosine kinase inhibitor, tyrphostin. MATERIALS AND METHODS Cell culture methodsIEC18 and IEC6 cells, related clones isolated from normal neonatal rat small intestine, were originally obtained from A Quaroni (Quaroni and May, 1980). In all assays these lines were used below passage 20. SW620 and HT29 human colon adenocarcinoma lines were obtained from the English Tissue Culture Collection (ETCC, Porton Down, Wilts, UK). All cells were maintained and passaged in Dulbecco's modified Eagles medium (DMEM) (GibcoBRL, Paisley, UK) containing 5% fetal calf serum (FCS) (Sigma, Poole, UK), 0.25 U ml -1 insulin (Hypurin, Fisons, Loughborough, UK), 100 U ml -1 penicillin and 30 µg ml -1 streptomycin (all Sigma, Poole, UK). Charcoal-stripped FCS, phenol red free DMEM, genistein, biochanin A, oestradiol, tamoxifen and tyrphostin 25 were a...

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Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells

Cited by 293 publications

References 23 publications

Grape-seed derived procyanidins interfere with adipogenesis of 3T3-L1 cells at the onset of differentiation

Grape-seed derived procyanidins interfere with adipogenesis of 3T3-L1 cells at the onset of differentiation

Modulation of Pro-survival Akt/Protein Kinase B and ERK1/2 Signaling Cascades by Quercetin and Its in Vivo Metabolites Underlie Their Action on Neuronal Viability

Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro

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