Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis

Zhang, Qiang; Zhao, Xin‐Huai

doi:10.1016/j.fct.2008.01.049

Cited by 170 publications

(125 citation statements)

References 52 publications

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“…Total flavonoids isolated from Korean citrus can arrest the A549 cells at G2/M-phase, and induce apoptosis via regulating the expression levels of caspase, cleaved PARP, and Bax/Bcl-xL (Park et al, 2012). Flavones and flavonols show in vitro anti-cancer activities to both human oesophageal adenocarcinoma and squamous cell carcinoma cells by inducting G2/M arrest and apoptosis (Zhang et al, 2008;Zhang et al, 2009). Artocarpesin, cycloartocarpesin, and isobavachalcone all have cytotoxic effects on the hepatocarcinoma HepG2, colon carcinoma HCT-116, leukemia CCRF-CEM, and other six cancer cells (Kuete et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Four in vitro activities of apigenin to human colorectal carcinoma cells susceptible to air-oxidative and heating treatments

Wang

Zhao

2017

Emir. J. Food Agric

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Section: Introductionmentioning

confidence: 99%

Four in vitro activities of apigenin to human colorectal carcinoma cells susceptible to air-oxidative and heating treatments

Wang

Zhao

2017

Emir. J. Food Agric

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“…PIG3 was discovered along with 12 other proteins in a serial analysis of gene expression studies designed to determine genes induced by p53 before the apoptosis onset (2). In addition, PIG3 expression can also be elicited by p63 and p73 (3), which are able to induce apoptosis in a p53-independent manner (4) and which are implicated in the induction of PIG3 through flavonoid exposure (5). PIG3 expression is largely regulated through its promoter (6), and polymorphisms within this site have been associated with invasive bladder cancer (7) and leukemia (8).…”

mentioning

confidence: 99%

Three-dimensional Structure and Enzymatic Function of Proapoptotic Human p53-inducible Quinone Oxidoreductase PIG3

Porté

Valencia

Yakovtseva

et al. 2009

Journal of Biological Chemistry

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Tumor suppressor p53 regulates the expression of p53-induced genes (PIG) that trigger apoptosis. PIG3 or TP53I3 is the only known member of the medium chain dehydrogenase/reductase superfamily induced by p53 and is used as a proapoptotic marker. Although the participation of PIG3 in the apoptotic pathway is proven, the protein and its mechanism of action were never characterized. We analyzed human PIG3 enzymatic function and found NADPH-dependent reductase activity with ortho-quinones, which is consistent with the classification of PIG3 in the quinone oxidoreductase family. However, the activity is much lower than that of -crystallin, a better known quinone oxidoreductase. In addition, we report the crystallographic structure of PIG3, which allowed the identification of substrate-and cofactor-binding sites, with residues fully conserved from bacteria to human. Tyr-59 in -crystallin (Tyr-51 in PIG3) was suggested to participate in the catalysis of quinone reduction. However, kinetics of Tyr/Phe and Tyr/Ala mutants of both enzymes demonstrated that the active site Tyr is not catalytic but may participate in substrate binding, consistent with a mechanism based on propinquity effects. It has been proposed that PIG3 contribution to apoptosis would be through oxidative stress generation. We found that in vitro activity and in vivo overexpression of PIG3 accumulate reactive oxygen species. Accordingly, an inactive PIG3 mutant (S151V) did not produce reactive oxygen species in cells, indicating that enzymatically active protein is necessary for this function. This supports that PIG3 action is through oxidative stress produced by its enzymatic activity and provides essential knowledge for eventual control of apoptosis.

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“…Quercetin, a well-investigated flavonoid, effectively inhibits cell proliferation and cell cycle progression and induces apoptosis in various cancer cells (14)(15)(16)(17). We previously reported that quercetin inhibits cell growth and induces apoptosis in MCF-7 cells through strong activation of AMPK that suppresses the expression of the anti-apoptotic molecule Cox-2 (18).…”

Section: Discussionmentioning

confidence: 99%

Regulation of mutual inhibitory activities between AMPK and Akt with quercetin in MCF-7 breast cancer cells

Lee

Park²

2010

Oncol Rep

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Abstract. In lieu of elucidating bidirectional connecting mechanism between AMP-activated protein kinase (AMPK) and survival signal Akt we applied MCF-7 breast cancer cells to determine whether AMPK modulation alters Akt signals and vice versa. Suppression of Akt activities with a synthetic Akt inhibitor alleviated AMPK activities suggesting that Akt is capable of inhibiting AMPK. Also the activation of AMPK with quercetin strongly abrogated Akt activities. Treating cancer cells with AMPK siRNA or Compound C resulted in marked increment of Akt dephosphorylation indicating that AMPK has antagonistic activities towards Akt. However, quercetin exerted Akt inhibitory activities in the absence of AMPK activation. Quercetin induced partial co-localization of phospho-Akt and phospho-AMPK in the nucleus even though their interaction seems to be indirect since the immunoprecipitation data indicate there was no direct binding between total Akt and AMPK. These results suggest there is a mutual suppressive interaction between AMPK and Akt. The investigation of mutual suppression between Akt and AMPK by chemo-preventive agents such as quercetin may provide a mechanistic rational for controlling breast tumor cell growth.

show abstract

Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis

Cited by 170 publications

References 52 publications

Four in vitro activities of apigenin to human colorectal carcinoma cells susceptible to air-oxidative and heating treatments

Four in vitro activities of apigenin to human colorectal carcinoma cells susceptible to air-oxidative and heating treatments

Three-dimensional Structure and Enzymatic Function of Proapoptotic Human p53-inducible Quinone Oxidoreductase PIG3

Regulation of mutual inhibitory activities between AMPK and Akt with quercetin in MCF-7 breast cancer cells

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