Geraniol and β-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity

Duncan, Robin E.; Lau, Dominic; El-Sohemy, Ahmed; Archer, Michael C.

doi:10.1016/j.bcp.2004.06.022

Cited by 144 publications

(113 citation statements)

References 37 publications

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“…Liu's study 9 reported that b-ionone at doses of 25-200 lmol/l inhibited cell proliferation and DNA synthesis in human mammary cancer MCF-7 cells in a dose-dependent manner. In a previous study, 13 b-ionone also inhibited the cell proliferation of MCF-7 cells via inhibition of Cdk2 activity and downregulation of cylins D1 and E. These results indicate that mechanisms other than impaired mevalonate synthesis mediate the antiproliferative and cell-cycle regulatory effects of b-ionone in human breast cancer cells. As a note, b-ionone could also inhibit the cell proliferation of the estrogen receptor negative cell line MDA MB 435 in the MAPK pathway by downregulation of ERK and MEK-1 expression and upregulation of JNK and MKP-1 expression.…”

Section: Expression Of Apoptosis Bcl-2 and Bax In Mammary Cancer Tissupporting

confidence: 61%

“…Physiological functions attributed to b-ionone include the inhibition of the growth of fungi 7 and the regulation of the synthesis of mevalonate-derived constituents. 8 In previous studies, b-ionone inhibited the growth of breast-, gastric-, colon-and HL-60-cancer cells in a dosedependent manner, [9][10][11][12][13] affected the MAPK pathway of MDA MB 435 cells, 14 and induced apoptosis of SGC-7901 gastric cancer cells and B16 murine tumor cells. 10,12 In addition, b-ionone could also affect metastasis in B16 and SGC-7901 cancer cell lines.…”

mentioning

confidence: 90%

“…Discussion b-Ionone, a pure isoprenoid, has been shown to possess potent antiproliferative activity 9,13,17 and to induce apoptosis 10,12 in cancer cells. Liu's study 9 reported that b-ionone at doses of 25-200 lmol/l inhibited cell proliferation and DNA synthesis in human mammary cancer MCF-7 cells in a dose-dependent manner.…”

Section: Expression Of Apoptosis Bcl-2 and Bax In Mammary Cancer Tismentioning

confidence: 99%

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β‐Ionone suppresses mammary carcinogenesis, proliferative activity and induces apoptosis in the mammary gland of the Sprague‐Dawley rat

Liu

Sun

Dong

et al. 2008

Intl Journal of Cancer

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b-Ionone demonstrates potent anticancer activity both in vitro and in vivo. We determined tumor incidence and the number of rats bearing tumors as well as cell proliferation and apoptosis in a rat mammary cancer model induced by 7, 12-dimethylbenz[a]anthracene (DMBA). Rats were fed an AIN-76A diet containing b-ionone (0, 9, 18 or 36 mmol/kg), starting 2 weeks before DMBA administration and continuing for 24 weeks. A dose-dependent inhibition of mammary carcinogenesis by dietary b-ionone was observed. Corresponding tumor incidence values were 82.1, 53.3, 25.9 and 10.0% (p < 0.01 or 0.05). Time to tumor appearance increased and tumor multiplicity decreased with increasing dietary b-ionone. Histopathological and immunohistochemical evaluations of tumors were performed on the 64, 31, 15 and 3 tumors, respectively, identified in rats from the respective groups of 30. The proportions of adenocarcinomas, adenomas and benign masses were equally distributed in the latter group. In proportions within the other groups, the proportions of adenocarcinomas and benign masses decreased and increased with increasing dietary b-ionone. Proliferating cell nuclear antigen (PCNA), cyclin D1 and Bcl-2 expression decreased, and Bax expression and nuclear fragmentation increased with increasing dietary b-ionone. These results demonstrate the potent capacity of dietary b-ionone to suppress DMBA-initiated mammary cancer in rats. ' 2008 Wiley-Liss, Inc.Key words: b-ionone; mammary carcinogenesis; cell proliferation; apoptosis Epidemiological studies have generally shown that the consumption of vitamin-rich fruits, vegetables and whole grains is inversely associated with risks for cancer and other chronic diseases. [1][2][3][4] Failing to demonstrate an inverse relationship between cancer incidence and consumption of the vitamins prominent in these plant products, investigators have turned attention to the many classes of nutrient phytochemical constituents also present in these foods. 5 Specific isoprenoids, culled from a group of some 22,000 products of secondary plant metabolic pathways sharing a common precursor, mevalonic acid, 6 have demonstrated anticarcinogenic and chemoprotective activities. One phytochemical compound, b-ionone, an end ring analog of b-carotenoid, represents a subclass of cyclic isoprenoids. Physiological functions attributed to b-ionone include the inhibition of the growth of fungi 7 and the regulation of the synthesis of mevalonate-derived constituents. 8 In previous studies, b-ionone inhibited the growth of breast-, gastric-, colon-and HL-60-cancer cells in a dosedependent manner, 9-13 affected the MAPK pathway of MDA MB 435 cells, 14 and induced apoptosis of SGC-7901 gastric cancer cells and B16 murine tumor cells. 10,12 In addition, b-ionone could also affect metastasis in B16 and SGC-7901 cancer cell lines. 11,12,15 Dietary studies reveal the chemopreventive 16 and antitumor 17 activities of b-ionone.This study confirms and extends observations of the chemopreventive impact of, and actions triggered, by diet...

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Section: Expression Of Apoptosis Bcl-2 and Bax In Mammary Cancer Tissupporting

confidence: 61%

mentioning

confidence: 90%

Section: Expression Of Apoptosis Bcl-2 and Bax In Mammary Cancer Tismentioning

confidence: 99%

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β‐Ionone suppresses mammary carcinogenesis, proliferative activity and induces apoptosis in the mammary gland of the Sprague‐Dawley rat

Liu

Sun

Dong

et al. 2008

Intl Journal of Cancer

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“…[13][14][15][16][17][18][19] Moreover, geraniol has been found to reduce the proliferative activity of Caco-2 human colon and MCF-7 human cancer cell lines. 20,21 In addition, lemongrass ethanolic extract, orally given to male Fischer 344 rats, inhibited colonic aberrant crypt foci (ACF) and glutathione S-transferase placental form-positive foci development induced by azoxymethane and diethylnitrosamine, respectively. 22,23 Despite of these data, there is no information about the beneficial action of LGEO oral treatment on carcinogeninduced target organ toxicity and early development of preneoplastic lesions in mice.…”

Section: Introduction Ementioning

confidence: 99%

Modifying Effects of Lemongrass Essential Oil on Specific Tissue Response to the Carcinogen N-Methyl-N-Nitrosurea in Female BALB/c Mice

Bidinotto

Costa²,

Costa³

et al. 2012

Journal of Medicinal Food

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Lemongrass (Cymbopogon citratus Stapf) essential oil has been used worldwide because of its ethnobotanical and medicinal usefulness. Regarding its medicinal usefulness, the present study evaluated the beneficial effects of lemongrass essential oil (LGEO) oral treatment on cell proliferation and apoptosis events and on early development of hyperplastic lesions in the mammary gland, colon, and urinary bladder induced by N-methyl-N-nitrosourea (MNU) in female BALB/c mice. The animals were allocated into three groups: G1, treated with LGEO vehicle for 5 weeks (five times per week); G2, treated with LGEO vehicle as for G1 and MNU (two injections each of 30 mg/kg of body weight at weeks 3 and 5); and G3, treated with LGEO (five times each with 500 mg/kg of body weight per week) and MNU as for G2. Twenty-four hours after the last MNU application, all animals were euthanized, and mammary glands, colon, and urinary bladder were collected for histological and immunohistochemical analysis.LGEO oral treatment significantly changed the indexes of apoptosis and/or cellular proliferation for the tissues analyzed. In particular, the treatment reduced the incidence of hyperplastic lesions and increased apoptosis in mammary epithelial cells. This increment in the apoptosis response may be related to a favorable balance in Bcl-2/Bax immunoreactivity in mammary epithelial cells. These findings indicate that LGEO presented a protective role against early MNU-induced mammary gland alterations in BALB/c mice.

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“…One mechanism of action proposed for the chemopreventive action of isoprenoids is related to the suppression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity (6,19), which is frequently elevated and deregulated in PNLs and neoplastic tissues (2). The inhibition of HMG-CoA reductase and intermediates of the mevalonate pathway is related to the suppression of cell proliferation and induction of apoptosis (2,6,20).…”

mentioning

confidence: 99%

Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

Vieira¹,

Heidor²,

Cardozo³

et al. 2011

Braz J Med Biol Res

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Geraniol and β-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity

Cited by 144 publications

References 37 publications

β‐Ionone suppresses mammary carcinogenesis, proliferative activity and induces apoptosis in the mammary gland of the Sprague‐Dawley rat

β‐Ionone suppresses mammary carcinogenesis, proliferative activity and induces apoptosis in the mammary gland of the Sprague‐Dawley rat

Modifying Effects of Lemongrass Essential Oil on Specific Tissue Response to the Carcinogen N-Methyl-N-Nitrosurea in Female BALB/c Mice

Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

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