Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells

Morley, K.; Ferguson, Peter J.; Koropatnick, James

doi:10.1016/j.canlet.2006.11.016

Cited by 210 publications

(149 citation statements)

References 41 publications

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“…On the other hand, there are a number of reports concerning a variety of biological effects of tangeretin and nobiletin, especially nobiletin, in addition to the concentrations of polymethoxy flavones in various species of citrus (10,11). For instances, direct and indirect evidences have been provided for anti-cancer effects (12)(13)(14)(15)(16)(17)(18)(19)(20), anti-inflammatory effects (21)(22)(23)(24), inhibition of NO production (25,26), enhancement of differentiation and lipolysis of adipocytes (27), prevention of cartilage destruction (28), improvement of memory impairment (29) and neurodegradation (30). However, no liver injury-suppressive effect of tangeretin and nobiletin has been reported yet.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Akachi

Shiina

Ohishi

et al. 2010

J Nutr Sci Vitaminol

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SummaryWe attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D -galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n -hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n -hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3 ′ ,4 ′ ,5,6,7,8-hexamethoxyflavanone (citromitin), 4 ′ ,5,6,7,8-pentamethoxyflavone (tangeretin) and 3 ′ ,4 ′ ,5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n -hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-␣ and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-␣ and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice. Key Words D -galactosamine, liver injury, shekwasha, Citrus depressa , flavonoids Fruits and vegetables are important as sources of several nutrients such as vitamins, minerals and dietary fibers. Fruits and vegetables also contain a variety of constituents, which are characteristic of the species of plant. It is widely recognized that relatively high intakes of fruits and vegetables are desirable for prevention of diseases and maintenance of healthy conditions ( 1 ). Previously we reported that several kinds of fruit had suppressive effects on D -galactosamine (GalN)-induced liver injury in rats when various kinds of lyophilized fruit were added to the diet ( 2 ). Furthermore, recently we found that some fruit juices, e.g., camu-camu and shekwasha, also had suppressive effects on GalNinduced liver injury in rats, and we identified the active compound (unpublished data). These findings indicate that certain fruits (and possibly vegetables) have a hepatoprotective effect in addition to nutritional effects.Since the liver is the central organ of many types of metabolism, the hepatoprotective effect of foods is worthwhile to investigate in detail, not only from the viewpoint of food science but also from the viewpoint of nutrition.In the present study, we attempted to isolate the constituent(s) res...

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Akachi

Shiina

Ohishi

et al. 2010

J Nutr Sci Vitaminol

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“…Another study showed that the compound induced G1 phase arrest on MDA-MB-435, MCF-7, and HT-29 cells (Morley et al, 2007). Hesperetin shows anticancer activity on MCF-7 cells through cell accumulation at G1 phase by inhibiting the expression of CDK2, CDK4 and Cyclin D; increasing the expression of p21 and p27; and increasing the binding of CDK4 and p21, but not p27 or p57 (Choi, 2007).…”

Section: Effect On Cell Cycle Regulationmentioning

confidence: 99%

“…This compound has been proven to inhibit the growth of estradiol-stimulated T47D cells (Van Slambrouck et al, 2005). Inhibition of MCF-7 cell proliferation was observed after 4 days treatment and G1 phase arrest after 24, 48, and 72 hours treatment, respectively (Morley et al, 2007).…”

Section: Effect On Cell Cycle Regulationmentioning

confidence: 99%

Natural Products for Cancer-Targeted Therapy: Citrus Flavonoids as Potent Chemopreventive Agents

Meiyanto

Hermawan²

2012

Asian Pacific Journal of Cancer Prevention

211

135

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One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer

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“…Other secondary metabolites of class of flavones, such as apigenin, luteolin and tangertin, with anticancer properties blocked the cell cycle either in the G 0 /G1 phase (33,34) or in the G 2 /M phase (35)(36)(37). Since most of the antineoplastic drugs in clinical use block the cell cycle in the S or G 2 /M phases whereas chrysin blocks the cell cycle in the G 1 phase, a combination of chrysin with currently used drugs might possibly improve melanoma therapies.…”

Section: Discussionmentioning

confidence: 99%

Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression

Canini¹

2010

Int J Oncol

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Abstract. Honey has long been used in medicine for different purposes. Only recently, however, its antioxidant property and preventive effects against different diseases, such as cancer, have been highlighted. Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in acacia honey. It has previously been shown to be an anti-tumor agent. In this study, we investigated the antiproliferative role of honey or chrysin on human (A375) and murine (B16-F1) melanoma cell lines. The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and the trypan blue exclusion test showed that both the tested compounds were able to induce an antiproliferative effect on melanoma cells in a dose-and time-dependent manner. Flow cytometry analysis indicated that cytotoxicity induced by honey or chrysin was mediated by G 0 /G 1 cell cycle arrest and induction of hyperploid progression. Our results suggest that the anti-proliferative effects of honey are due mainly to the presence of chrysin. Chrysin may therefore be considered a potential candidate for both cancer prevention and treatment. Further investigation is needed to validate the contribution of chrysin in tumor therapy in vivo.

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Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells

Cited by 210 publications

References 41 publications

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Natural Products for Cancer-Targeted Therapy: Citrus Flavonoids as Potent Chemopreventive Agents

Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression

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