The present study was designed to investigate a possible way by which garlic and mistletoe extracts can help inhibit breast cancer invasion and restore cell differentiation. Identification of agents that delay the onset or progression of breast cancer and that are not toxic is desirable. Poor prognosis of breast cancer is associated with cancer cell invasion and metastasis and epithelial-mesenchymal transition is a crucial event in the tumor invasion process. The authors recently demonstrated that signal transducers and activators of transcription 5a (Stat5a) and its Janus tyrosine kinase, (Jak2), suppress invasion and promote human breast cancer cell differentiation by means of inhibition of epithelial-to-mesenchymal dedifferentiation. In the present study, the authors used a combination of Jak2/Stat5a overexpression and histone deacetylase (HDAC) inhibitors (which inhibit proliferation and induce differentiation ), mistletoe (Viscum album) plant extract, and/or diallyl trisulfide (a component of garlic) as an alternative way to inhibit breast cancer invasion and restore differentiation in vitro and in vivo. The investigation included a panel of human breast cancer cell lines that display different phenotypic and differentiation patterns (ranging from poor to high differentiation), including MDA-231, MDA-468, T-47D, MCF-7, BT-20, SKBr3, and ZR-75-1 cell lines. Cells were pretreated with or without HDAC inhibitors, as well as mistletoe plant extract and/or diallyl trisulfide, and then either mock infected or actually infected with adenovirus carrying Wild type (Wt-Jak2), Wt-Stat5a, Dominant negative (Dn-Stat5), or a combination of Wt-Jak2 and Wt-Stat5a. Pretreatment with HDAC inhibitors, mistletoe plant extract, and /or diallyl trisulfide was found to act synergistically with co-expression of Wt-Jak2/Stat5a to promote epithelial differentiation. The combination induced reduced cell motility and invasiveness. In further experimentation, xenograft tumors of MDA-231 (ER-/PR-) and T-47D (ERα+) cell lines were implanted in nude mice. After four weeks, the growth of MDA-231 and T-47D tumors that co-expressed Wt-Jak2/Stat5a were found to be inhibited by 45.4% and 51.12%, respectively, compared to the untreated control group (t=2.410, P<0.05) and by 48.3% and 54.33%, respectively, compared to the tumors expressing Dn-Stat5 group (t=1.994, P<0.05). In addition, pretreatment with HDAC inhibitors and/or diallyl trisulfide was found to significantly inhibit the growth of MDA-231 and T-47D tumors expressing Wt-Jak2/Stat5a compared to the tumors expressing Wt- Stat5a or Wt-Jak2 alone. The authors comment that the findings suggest that a combination of Jak2/Stat5a overexpression and nontoxic agents can delay onset or progression of breast cancer by restoring lost differentiation of breast cancer through epithelial-mesenchymal transition inhibition. This offers a potential new therapeutic strategy to inhibit human breast cancer progression.

The present study was designed to investigate whether aged garlic has protective effects against doxorubicin-induced free radical production and cardiotoxicity in male rats. Doxorubicin (Adriamycin), a highly active chemotherapy agent, can cause severe cardiotoxic side effects associated with increased oxidative stress and apoptosis. A single dose of doxorubicin (25 mg/kg) was found to increase both serum cardiac enzymes LDH and CPK activities and malondialdhyde (MDA) in plasma. However, rats pretreated with aged garlic extract (250 mg/kg) for 27 days before being administered doxorubicin were found to have reduced activity of both enzymes, and a significantly reduced production of MDA in plasma. In addition, total antioxidant activity was found to be increased after aged garlic extract administration. Histopathological examination of rat heart tissue demonstrated that doxorubicin resulted in cardiac tissue structure changes, namely, peri arterial fibrosis and apoptotic changes in cardiomyocytes. The aged garlic extract pretreatment regimen reduced the negative effects of doxorubicin on cardiac tissue; the cardiomyocytes appeared more or less similar to cardiac tissue of control rats. However, vascular dilatation, mild congestion and interstitial edemas were still observed in the aged garlic plus doxorubicin treated rats. The authors conclude that aged garlic extract may be protective against doxorubicin-induced cardiotoxicity.

The present study was designed to evaluate the action of diallyl disulfide, a component of garlic, in human mammary (MCF-7) cancer cells. Diallyl disulfide was found to inhibit the proliferation of MCF-7 cells. It also caused the apoptotic ratio to increase rapidly; the authors conclude that diallyl disulfide induces apoptosis of MCF-7 breast cancer cells.

Persian shallot (Allium hirtifolim) is a member of the allium genus (alliaceae family). The current study investigated the in vitro effects of a chloroformic extract of Persian shallot and its allicin on the proliferation of HeLa (cervical cancer), MCF-7 (hormone receptor positive breast cancer) and L929 (mouse connective) cells. The shallot extract inhibited proliferation of the tumor cell lines. The inhibition in the MCF-7 and HeLa cell lines was dose dependent. DNA fragmentation analysis demonstrated a large number of apoptotic cells in the treated HeLa and MCF-7 cell groups, but no effects in the L929 cells.

The current case-control study was designed to compare the diets of a group of Korean breast cancer patients with a healthy control group. The cases included 97 women with newly confirmed diagnoses of breast cancer at the inpatient or outpatient clinic of Yeouido St. Mary’s Hospital in Seoul, and excluded women with any history of liver diseases, diabetes mellitus, respiratory disorders and cardiovascular diseases. The 97-person control group also excluded women with known malignant, hormonal, gynecological or endocrine diseases. Intake of nutrients in 117 food items were estimated in the breast cancer patients and age-matched healthy controls using a quantitative food frequency questionnaire administered by a trained dietitian. The questionnaire also included general information (age, sex and marital status), age at menarche, and pregnancy history. It was found that the average caloric intake of the breast cancer patients and the healthy controls did not differ significantly. However, the breast cancer patients consumed significantly less fat and antioxidant nutrients such as vitamin A, retinol, beta-carotene, vitamin C and vitamin E than did the controls. Consumption of eggs (p<0.01), legumes (p<0.05), vegetables (p<0.05), seasonings (p<0.001), and oils and fats (p<0.01) was significantly lower in the breast cancer patients. However, the level of energy from fat is relatively low in Korean patients compared to their Western counterparts, and fat consumption may not be an independent risk factor at this level of intake. With respect to particular foods, in addition to eggs, the breast cancer patients consumed a significantly lower quantity of bean curd (tofu), onion, garlic, green pepper, sweet pepper, kale, cucumber, seasoned bean sprouts, sesame leaf, zucchini, radish, mushroom, crown daisy, red pepper paste, bean paste, spicy bean paste, orange juice, grape juice, and tomato juice than the controls. On the other hand, the breast cancer patients consumed significantly greater quantities of cooked rice, noodles, deep fried chicken, satsuma mandarin, Korean melon, kimchi and coffee than the controls. The authors conclude that since the breast cancer patients consumed less soy and vegetables, they had a lower intake than the controls of rich sources of antioxidant nutrients, phytosterols, fiber and non-nutritional components that may reduce the risk of cancer. In addition, the breast cancer patients in this study consumed lower quantities of red pepper paste, bean paste and spicy bean paste, causing their intake of pepper flavonols (which may have a protective effect on breast cancer risk) to be lower than that of the controls.

The current study was designed to investigate the role of allium vegetables in the etiology of various cancers using data from an integrated network of Italian and Swiss case-control studies. The relationship between the frequency of onion and garlic use and the cancers was estimated using multivariate logistic regression models that were adjusted for energy intake and other cancer-related factors. The consumption of onions was found to vary between 0-14 portions per week among cancer cases and 0-22 portions among controls. The odds ratios for the highest category of onion and garlic intake were 0.16 and 0.61 for cancer of the oral cavity and pharynx, 0.12 and 0.43 for esophageal cancer, 0.44 and 0.74 for colorectal cancer, 0.17 and 0.56 for laryngeal cancer, 0.75 and 0.90 for breast cancer, 0.27 and 0.78 for ovarian cancer, 0.29 and 0.81 for prostate cancer, and 0.62 and 0.69 for renal cell cancer. The authors conclude that this large southern European population data set demonstrates an inverse association between the frequency of use of allium vegetables and the risk of several common cancers.

Garlic supplementation by cancer patients is common. The current study evaluates the influence of garlic on the pharmacokinetics of docetaxel, a chemotherapy drug. Ten women with breast cancer were treated with docetaxel given weekly for three or four weeks. Three days after the initial dose of docetaxel, the patients received 600 mg of garlic twice daily for 12 consecutive days. The mean baseline clearance of docetaxel was 30.8 L/h/m2 [95% confidence intervals (95% CI), 16.7-44.9]. Coadministration of garlic reduced mean clearance of docetaxel to 23.7 L/h/m2 (95% CI, 15.5-31.8) and 20.0 L/h/m2 (95% CI, 13.3-26.7) on days 8 and 15, respectively. Additional pharmacokinetic variables of docetaxel, including peak concentration, area under the curve, volume of distribution, and half-life, also were not statistically significantly different. The mean area under the curve ratio between day 15 and day 1 was 3.74 in three individuals with the CYP3A5*1A/*1A genotype (all African American) compared with 1.02 in six individuals with the CYP3A5*3C/*3C genotype (all Caucasian). The authors conclude that garlic does not significantly affect the disposition of docetaxel. However, it garlic might decrease the clearance of docetaxel in patients carrying a CYP3A5*1A allele.

The present study investigated the potential relationship between flavonoid consumption and risk of breast cancer. Dietary information was collected in a large study conducted in Italy between 1991 and 1994, including 2,569 women with breast cancer and 2,588 hospital controls. After allowing for major confounding factors and energy intake, risk of breast cancer was found to be reduced for increasing intake of flavones (e.g., apigenin, luteolin, tangeritin) and flavonols (e.g., fisetin, quercetin, myricetin, kaempferol). No significant association was found for other flavonoids, including flavanones, flavan-3-ols, anthocyanidins, as well as for isoflavones. These findings confirm the results of a previous Greek study.

Diethylstilbestrol (DES), a synthetic estrogen, can cause breast cancer in humans and in female ACI rats. To test the hypothesis that diallyl sulfide will alter the expression of genes responsible for the metabolism of DES, male Sprague Dawley rats were divided into the following four groups: (1) corn oil (control group), (2) 50 mg/kg DES, (3) 50 mg/kg diallyl sulfide, and (4) 50 mg/kg diallyl sulfide plus 50 mg/kg DES. The animals were sacrificed on day five and breast tissue was removed for analysis. DES, diallyl sulfide, and DES/diallyl sulfide treatments increased the expression of CYP1A1 by four-, six-, and 13-fold, respectively compared to the control. A similar trend was seen for CYP1B1. Diallyl sulfide increased the expression of glutathione-S-transferase by 19-fold, whereas DES decreased the expression of glutathione-S-transferase. The authors conclude that diallyl sulfide may prevent the formation of DNA adducts partly by increasing the expression of phase II metabolizing genes in the breasts of female ACI rats.

Food frequency questionnaires were given to 90,630 women in the Nurses Health Study II in 1991 and 1995 to evaluate the association of flavonol intake with breast cancer risk in premenopausal women who were between 26 and 46 years at baseline in 1991. During eight years of follow-up, there were 710 cases of invasive breast cancer. There were no associations seen between consumption of individual flavonols such as kaempferol, quercetin or myricetin and breast cancer risk. The multivariate RR, comparing highest to lowest quintiles of cumulative average flavonol intake, was 0.94 for sum of flavonol-rich foods. Among the major food sources of flavonols, the authors found a significant inverse association of breast cancer with intake of beans and lentils but not with tea, onions, apples, string beans, broccoli, green pepper or blueberries.

The present study was designed to characterize the differences in the flavonoid content of various types of onions. Shallots and 10 common U.S. onion varieties (Western Yellow, Northern Red, New York Bold, Western White, Peruvian Sweet, Empire Sweet, Mexico, Texas 1015, Imperial Valley Sweet, and Vidalia) were assessed for total flavonoid and phenolic contents and antiproliferative and antioxidant activities. Shallots were found to have the highest total phenolic content (114.7 ± 10.0 mg/100 g), which was six times the content of the Vidalia onion, which had the lowest phenolic content. The Western Yellow onion was found to have the highest total flavonoid content (69.2 ± 3.7 mg/100 g), which was 11 times that of the Western White onion (with the lowest flavonoid content). Shallots had the highest total antioxidant activity (45.5 ± 2.1 μmol of vitamin C equiv/g), followed by the Western Yellow, New York Bold, Northern Red, Mexico, Empire Sweet, Western White, Peruvian Sweet, Texas 1015, Imperial Valley Sweet, and Vidalia onions. Both total phenolic content and total flavonoid content were strongly correlated with the total antioxidant activity for all varieties. The proliferation of HepG2 (liver cancer) and Caco-2 (colon cancer) cells was significantly inhibited in a dose-dependent manner after exposure to Western Yellow, shallot, New York Bold, and Northern Red extracts. However, the Western White, Peruvian Sweet, Empire Sweet, Mexico, Texas 1015, Imperial Valley Sweet, and Vidalia onions had weak antiproliferative activity against both HepG2 and Caco-2 cell lines.

Apigenin, a common flavonoid, is found in many fruits and vegetables, including Chinese cabbage, bell pepper, garlic, celery and guava. Although some flavonoids are mutagenic, apigenin has been found to have no mutagenic activity and, in fact, apigenin exhibits anti-proliferative activity against human breast cancer cells. In the present study, apigenin activity in human breast cancer cell lines having different levels of HER2/neu expressions was examined. It was found that apigenin exhibited potent growth-inhibitory effects in HER2/neu-overexpressing breast cancer cells but was much less powerful for those cells expressing basal levels of HER2/neu. Proapoptic activity was also observed in HER2/neu-overexpressing cells in a dose- and time-dependent manner. A cell survival pathway involving phosphatidylinositol 3-kinase and Akt is known to play a significant role in preventing apoptosis in HER2/neu-overexpressing breast cancer cells. The study results found that apigenin inhibits Akt function in tumor cells in a complex manner.

The current study examined the effect of diallyl disulfide, an organosulfur compound found in garlic, on the growth of estrogen receptor positive (ER+) KPL-1 and MCF-7 and estrogen receptor negative (ER-) MDA-MB-231 and MKL-F human breast cancer cell lines. After 72 hour incubation, diallyl disulfide caused inhibition of growth (due to apoptosis) in all four cell lines regardless of ER status. In MDA-MB-231 cells, diallyl disulfide antagonized the effects of linoleic acid, a strong breast cancer cell stimulator, and synergized the effects of eicosapentaenoic acid, a strong breast cancer cell suppressor. The authors conclude that diallyl disulfide could be a promising anticancer agent for both hormone-dependent and -independent breast cancers.

In the current study, 198 Mexico City women aged 21 to 79 years with breast cancer were individually age matched to 198 women with no breast disease from 1994 to 1995. Information on socioeconomic characteristics and diet was obtained by interview and a questionnaire was used to estimate the level of consumption of 95 foods. The effect of selected foods on risk of breast cancer was estimated using logistic regression models. The adjusted odds ratio for the consumption of more than one slice of onion per day and breast cancer was 0.27 (95% confidence interval = 0.16-0.47), and had a statistically significant trend (p < 0.001). This protective effect remained after adjustment for known breast cancer risk factors. For premenopausal women, there was also a protective and significant effect associated with the intake of lettuce and spinach and nonsignificant protective effects for apples and herbal tea.