Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells

Chen, Di; Daniel, Kenyon G.; Chen, Marina S.; Kuhn, Deborah J.; Landis-Piwowar, Kristin R.; Dou, Q. Ping

doi:10.1016/j.bcp.2005.02.022

Cited by 294 publications

(293 citation statements)

References 40 publications

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“…Chen et al (94) examined the flavonoids viz. apigenin, quercetin, kaempferol and myricetin for their proteasomeinhibitory and apoptosis-inducing abilities in human leukemia cells.…”

Section: Apigenin and Leukemiamentioning

confidence: 99%

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Patel

Shukla²,

Gupta³

2007

Int J Oncol

314

362

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Abstract. Cancer is one of the major public health burdens in the United States and in other developed countries, causing approximately 7 million deaths every year worldwide. Cancer rates vary dramatically in different regions and populations around the globe, especially between developing and developed nations. Changes in cancer prevalence patterns occur within regions as their populations age or become progressively urbanized. Migration has also contributed to such variations as changes in dietary habits influence cancer rates. These epidemiologic findings strongly suggest that cancer rates are influenced by environmental factors including diet, which is largely preventable. Approaches to prevent cancer include overlapping strategies viz. chemoprevention or dietary cancer prevention. Chemoprevention aims at prevention or reversal of the initiation phase of carcinogenesis or arrest at progression of carcinogenesis through the administration of naturally occurring constituents or pharmacological agents. Cancer prevention through diet may be largely achievable by increased consumption of fruits and vegetables. Considerable attention has been devoted to identifying plant-derived dietary agents which could be developed as promising chemopreventives. One such agent is apigenin. A naturally occurring plant flavone (4', 5, 7,-trihydroxyflavone) abundantly present in common fruits and vegetables including parsley, onions, oranges, tea, chamomile, wheat sprouts and some seasonings. Apigenin has been shown to possess remarkable anti-inflammatory, antioxidant and anti-carcinogenic properties. In the last few years, significant progress has been made in studying the biological effects of apigenin at cellular and molecular levels. This review examines the cancer chemopreventive effects of apigenin in an organ-specificity format, evaluating its limitations and its considerable potential for development as a cancer chemopreventive agent.

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“…Chen et al (94) examined the flavonoids viz. apigenin, quercetin, kaempferol and myricetin for their proteasomeinhibitory and apoptosis-inducing abilities in human leukemia cells.…”

Section: Apigenin and Leukemiamentioning

confidence: 99%

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Patel

Shukla²,

Gupta³

2007

Int J Oncol

314

362

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“…After 2 h incubation at 37 °C, inhibition of the proteasomal chymotrypsin-like activity was measured (Chen et al, 2005b).…”

Section: Synthesis Of Bis(1-pyrrolidinecarbodithioato-ksks′)copper(imentioning

confidence: 99%

“…The prepared whole cell extracts (30 μg per sample) were then incubated with 40 μM of Ac-DEVD-AMC in 100 μL assay buffer at 37 °C for at least 2 h. The release of the AMC groups was measured as previously described (Chen et al, 2005b).…”

Section: Synthesis Of Bis(1-pyrrolidinecarbodithioato-ksks′)copper(imentioning

confidence: 99%

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Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity

Milacic

Chen

Giovagnini

et al. 2008

Toxicology and Applied Pharmacology

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144

128

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Zinc and copper are trace elements essential for proper folding, stabilization and catalytic activity of many metalloenzymes in living organisms. However, disturbed zinc and copper homeostasis is reported in many types of cancer. We have previously demonstrated that copper complexes induced proteasome inhibition and apoptosis in cultured human cancer cells. In the current study we hypothesized that zinc complexes could also inhibit the proteasomal chymotrypsin-like activity responsible for subsequent apoptosis induction. We first showed that zinc(II) chloride was able to inhibit the chymotrypsin-like activity of a purified 20S proteasome with an IC 50 value of 13.8 μM, which was less potent than copper(II) chloride (IC 50 5.3 μM). We then compared the potencies of a pyrrolidine dithiocarbamate (PyDT)-zinc(II) complex and a PyDT-copper(II) complex to inhibit cellular proteasomal activity, suppress proliferation and induce apoptosis in various human breast and prostate cancer cell lines. Consistently, zinc complex was less potent than copper complex in inhibiting the proteasome and inducing apoptosis. Additionally, zinc and copper complexes appear to use somewhat different mechanisms to kill tumor cells. Zinc complexes were able to activate calpain-, but not caspase-3-dependent pathway, while copper complexes were able to induce activation of both proteases. Furthermore, the potencies of these PyDT-metal complexes depend on the nature of metals and also on the ratio of PyDT to the metal ion within the complex, which probably affects their stability and availability for interacting with and inhibiting the proteasome in tumor cells.

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“…Moreover, flavonoids exert specific cytotoxic activity towards cancer cells which has generated large interest in devel-0939Ð5075/2008/0500Ð0347 $ 06.00 " 2008 Verlag der Zeitschrift für Naturforschung, Tübingen · http://www.znaturforsch.com · D oping flavonoid-based cytostatics for anticancer therapy (Galati and O'Brien, 2004). Different mechanisms are linked to flavonoid-mediated cytotoxicity, including proteasome inhibition (Chen et al, 2005), inhibition of fatty acid synthesis (Brusselmans et al, 2005), topoisomerase inhibition (Constantinou et al, 1995), inhibition of phosphatidyl-inositol 3-kinase (Agullo et al, 1997), induction of cell cycle arrest (Lepley et al, 1996), induction of p53 (Plaumann et al, 1996) or enhanced expression of c-fos and c-myc proto-oncogenes (Chen et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

In vitro Cytotoxic Activity of Salsola oppositifolia Desf. (Amaranthaceae) in a Panel of Tumour Cell Lines

Tundis

Loizzo

Bonesi

et al. 2008

Zeitschrift Für Naturforschung C

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The aim of the present study was to evaluate for the first time the in vitro cytotoxic activity of fractions and isolated flavonols from Salsola oppositifolia Desf. (Amaranthaceae). The nhexane fraction demonstrated an effective cytotoxic activity on the large lung carcinoma and amelanotic melanoma cell lines with IC 50 values of 19.1 μg/ml and 24.4 μg/ml, respectively. Also the dichloromethane fraction exhibited cytotoxic activity against COR-L23 (IC 50 30.4 μg/ml) and C32 (IC 50 33.2 μg/ml) cells, while the EtOAc fraction demonstrated a selective cytotoxic activity against MCF-7 cells (IC 50 67.9 μg/ml). The major active constituents of this fraction were isorhamnetin-3-O-glucoside (1) and isorhamnetin-3-O-rutinoside (2), which showed an interesting activity against the cell line MCF-7 with IC 50 values of 18.2 and 25.2 μg/ml, respectively. Compound 2 exhibited a strong activity against the hormonedependent prostate carcinoma LNCaP cell line with an IC 50 of 20.5 μg/ml. Constituents of S. oppositifolia were identified by GC-MS and NMR analyses.

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Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells

Cited by 294 publications

References 40 publications

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity

In vitro Cytotoxic Activity of Salsola oppositifolia Desf. (Amaranthaceae) in a Panel of Tumour Cell Lines

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