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

Abstract

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...

Comparative study on the essential oils of Myosotis arvensis and Myosotis palustris herbs (Boraginaceae)

“…Other compound with anticancer potential is b-ionone, unsaturated cyclic ketone present in M. palustris oil. Its ability of mammary cancer suppression was proved in the study conducted in rats (Liu et al 2008).…”

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

“…To the best of our knowledge, in vivo studies of chemoprevention with GO have only been conducted in liver, breast and pancreas carcinogenesis models, with inhibition of hepatic PNLs (9,10) and mammary (11,34) and pancreatic (12) neoplastic lesions, respectively. Recently, βI was reported to have chemopreventive activity in liver (8,10), breast (3,11) and colon (14) carcinogenesis. However, inhibition of total ACF and of ACF <4 or ACF ≥4 crypts by βI was not observed in the present study.…”

“…Bioactive compounds present in foods, such as isoprenic derivatives found in fruits and vegetables, are potential chemopreventive agents against cancer (2,3). Promising dietary isoprenoids are β-ionone (βI), a cyclic isoprenoid, the product of β-carotene degradation, which is present mainly in grapes and wine aromatizers, and geraniol (GO), an acyclic monoterpene, which is an important constituent of the essential oils of ginger, lemon, lime, orange, and nutmeg ( Figure 1).…”

Quantification and potential aroma contribution of β‐ionone in marine salt

“…chemopreventive and antitumor activities. [14] The volatile organic compound β-ionone, detected in the inorganic matrix of marine salt, is a biomarker that could arise from both natural (e.g. algae, bacteria) and non-natural sources (e.g.…”