The growth of many breast tumors is stimulated by IGF-1, which activates signal transduction pathways inducing cell proliferation. $ER{\alpha}$ is important in this process. The aim of the study was to investigate relationships in vitro among inhibitory effects of luteolin on the growth of MCF-7 cells, IGF-1 pathway and $ER{\alpha}$. Our results showed that luteolin could effectively block IGF-l-stimulated MCF-7 cell proliferation in a dose- and time-dependent manner and block cell cycle progression and induce apoptosis evidenced by the flow cytometric detection of sub-G1DNA content. Luteolin markedly decreased IGF-l-dependent IGF-IR and Akt phosphorylation without affecting Erk1/2 phosphorylation. Further experiments pointed out that $ER{\alpha}$ was directly involved in IGF-l induced cell growth inhibitory effects of luteolin, which significantly decreased $ER{\alpha}$ expression. Knockdown of $ER{\alpha}$ in MCF-7 cells by an $ER{\alpha}$-specific siRNA decreased the IGF-l induced cell growth inhibitory effects of luteolin. $ER{\alpha}$ is thus a possible target of luteolin. These findings indicate that the inhibitory effect of luteolin on the growth of MCF-7 cells is via inhibiting IGF-l mediated PI3K-Akt pathway dependent of $ER{\alpha}$ expression.
Choi, Won Jun;Kim, Jong Hyuk;Han, Gi Ppeum;Kwon, Chan Ho;Kil, Dong Yong
Animal Bioscience
/
v.34
no.7
/
pp.1181-1192
/
2021
Objective: The objective of the current study was to investigate the effects of dietary hatchery by-products (HBPs) as a replacement of fish meal (FM) on growth performance, relative organ weight, plasma measurements, immune organ index, meat quality, and tibia characteristics of broiler chickens. Methods: A total of 720 broiler chickens (3 d of age) were randomly allotted to 1 of 9 treatments with 8 replicates. Each replicate consisted of 5 male and 5 female birds. The basal diet was formulated to contain 5.0% commercial FM, whereas eight treatment diets were prepared by replacing 25%, 50%, 75%, or 100% of FM in the basal diet with infertile eggs (IFE) or a mixture of various HBPs (MIX); therefore, the inclusion levels of IFE or MIX in the experimental diets were 1.25%, 2.50%, 3.75%, or 5.00%. The diets and water were provided on an ad libitum basis for 32 d. Results: Increasing inclusion levels of IFE as a replacement of FM in diets had no effects on growth performance, plasma measurements, immune organ index, and tibia characteristics of broiler chickens. Increasing inclusion levels of IFE in diets increased (linear, p<0.05) meat lightness (L*) but decreased (linear, p<0.05) meat redness (a*). The breast meat pH at 1-h postmortem was increased (linear, p<0.05) by increasing inclusion levels of IFE in diets. Likewise, increasing inclusion levels of MIX in diets had no effects on growth performance, relative organ weight, plasma measurements, immune organ index, and tibia characteristics. However, increasing inclusion levels of MIX in diets increased (linear, p<0.05) 1-h postmortem pH but decreased (linear, p<0.05) 24-h postmortem pH of breast meat. Increasing inclusion levels of MIX in diets decreased (linear, p<0.05) thiobarbituric acid reactive substances values of breast meat. Conclusion: Both IFE and MIX are suitable alternatives to FM as protein ingredients in broiler diets.
Kim, Jin;Lee, Yoon Hee;Yoon Park, Jung Han;Sung, Mi-Kyung
Nutrition Research and Practice
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v.9
no.6
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pp.628-636
/
2015
BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.
The experiment was carried out to investigate the effects of Alisma canaliculatum with probiotics (ACP) on the growth performance, meat composition, oxidative stability, and fatty acid composition of broiler meat. Sixteen probiotic strains were tested for their levels of acid, bile, and heat tolerance. Among them, Lactobacillus acidophilus KCTC 3111, Enterococcus faecium KCTC 2022, Bacillus subtilis KCTC 3239, and Saccharomyces cerevisiae KCTC 7928 were selected for use in ACP. Exactly 140 Ross broiler chicks were assigned to four dietary treatments in five replications for 5 wks in a completely randomized design. The dietary treatments were NC (Negative control; basal diet), PC (Positive control; basal diet with 0.005% Chlortetracycline), ACP-0.5% (basal diet with 0.5% ACP powder), and ACP-1% (basal diet with 1% ACP powder). According to the results, body weight of the broilers increased, and feed conversion ratio improved in the ACP-0.5% group compared to the NC group (p<0.05). Crude protein content of breast meat was higher (p<0.05) in the ACP-0.5% group, whereas crude fat content of thigh meat was lower (p<0.05) in the supplemented groups. Breast meat absolute and relative weights were both higher (p<0.05) in the ACP groups compared to the control group. Further, ACP diets increased gizzard and decreased large intestine relative weights, whereas kidney relative weight decreased upon the addition of a higher level (1%) of ACP (p<0.05). Thiobarbituric acid reactive substances values of breast and thigh meats were reduced (p<0.05) by ACP supplementation compared to control. Regarding the fatty acid composition of breast meat, arachidonic acid, docosahexaenoic acid, PUFA, and n6 fatty acid levels decreased (p<0.05) in the ACP groups, whereas the levels of linoleic acid, PUFA, PUFA/SFA, and n6 fatty acid in thigh meat decreased (p<0.05) by ACP and PC diets. It can be suggested based on the study results that ACP-0.5% diet could be an effective feed additive for broilers.
This experiment was conducted to evaluate the effects of dietary olive oil on growth performance, carcass parameters, serum characteristics, and fatty acid composition of breast and drumstick meat in broiler chickens. A total of 480 broilers were randomly allotted into three dietary treatments, including T (basal diet, 5% tallow), O1 (2% olive oil+3% tallow), and O2 (5% olive oil). During d 0 to 21, broilers fed the diet supplemented with 5% olive oil showed lower (p<0.05) body weight gain (BWG) and feed intake (FI) compared with those fed the T diet. Serum triglyceride concentration was reduced (p<0.05), while high density lipoprotein (HDL)-cholesterol concentration was increased (p<0.05) in the O2 treatment group compared with the T and O1 treatment groups. The addition of olive oil to the diets induced a reduction (p<0.05) in the total saturated fatty acid (SFA) contents in breast and drumstick meat, and increased (p<0.05) the total unsaturated fatty acid (USFA) contents and USFA/SFA ratios. In conclusion, a diet with 5% olive oil could decrease BWG and FI of broilers during the starter period (wk 0 to 3), and cause an increase in the serum HDL-cholesterol level, while decreasing the serum triglyceride concentration. Furthermore, USFA level and USFA/SFA ratios in breast and drumstick meat were increased by dietary supplementation of 2 or 5% olive oil.
We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of ${\beta}-catenin$ in C2C12 cells. However, the relationship between EGF-induced SMURF1 and ${\beta}-catenin$ expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate ${\beta}-catenin$ expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of ${\beta}-catenin$ mRNA and protein. Overexpression of SMURF1 downregulated ${\beta}-catenin$ mRNA and protein, whereas knockdown of SMURF1 increased ${\beta}-catenin$ expression and blocked EGF-induced ${\beta}-catenin$ downregulation. Knockdown of ${\beta}-catenin$ enhanced cell migration and invasion of MDAMB231 cells, while ${\beta}-catenin$ overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of ${\beta}-catenin$ enhanced vimentin expression and decreased cytokeratin expression, whereas ${\beta}-catenin$ overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates ${\beta}-catenin$ in a SMURF1-dependent manner and that ${\beta}-catenin$ downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.
Park, Jae Eun;Kim, Hyeon Woo;Yun, Sung Hwan;Kim, Sun Jung
Journal of Ginseng Research
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v.45
no.6
/
pp.754-762
/
2021
Background: Ginsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anti-cancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse. Methods: LncRNAs whose promoter DNA methylation level was significantly altered by Rh2 were screened from methylation array data. The effect of STXBP5-AS1, miR-4425, and RNF217 on the proliferation and apoptosis of MCF-7 breast cancer cells was monitored in the presence of Rh2 after deregulating the corresponding gene. The ceRNA relationship between STXBP5-AS1 and miR-4425 was examined by measuring the luciferase activity of a recombinant luciferase/STXBP5-AS1 plasmid construct in the presence of mimic miR-4425. Results: Inhibition of STXBP5-AS1 decreased apoptosis but stimulated growth of the MCF-7 cells, suggesting tumor-suppressive activity of the lncRNA. MiR-4425 was identified to have a binding site on STXBP5-AS1 and proven to be downregulated by STXBP5-AS1 as well as by Rh2. In contrast to STXBP5-AS1, miR-4425 showed pro-proliferation activity by inducing a decrease in apoptosis but increased growth of the MCF-7 cells. MiR-4425 decreased luciferase activity from the luciferase/STXBP5-AS1 construct by 26%. Screening the target genes of miR-4425 and Rh2 revealed that Rh2, STXBP5-AS1, and miR-4425 consistently regulated tumor suppressor RNF217 at both the RNA and protein level. Conclusion: LncRNA STXBP5-AS1 is upregulated by Rh2 via promoter hypomethylation and acts as a ceRNA, sponging the oncogenic miR-4425. Therefore, Rh2 controls the STXBP5-AS1/miR-4425/RNF217 axis to suppress breast cancer cell growth.
Background: Breast cancer is a heterogeneous disease that represents a major public health problem. The immunohistochemical determination of breast cancer subtypes with regard to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status can contribute to improved selection of therapy and patientcare. The purpose of this study was to determine the prevalence of the molecular breast cancer subtypes and to assess their associations with classical clinicopathologic parameters for better therapeutic decisions in women with breast cancer in the Ivory Coast. Materials and Methods: Formalin-fixed and paraffin-embedded blocks of patients diagnosed with primary breast carcinoma were subjected to immunohistochemical assay for the assessment of ER/RP and HER2 expression. The one-way analysis of variance evaluated the difference between breast cancer subtypes and mean age of patients. The Chi-square Test was used to compare standard clinicopathologic prognostic parameters with tumor subtypes. Results. Among 302 patients, 57% were premenopausal and 43% were postmenopausal. The invasive ductal carcinoma not otherwise specified (IDC NOS) (82.8%) was the most frequent histological type, and the tumor grade 2 (56%) was predominant followed by grade 3 (20.9%). The proportion of positivity of ER, PR, and HER2 was 56%, 49%, and 15.6%, respectively. Half of patients of this study (51.6%) had luminal A breast tumor type followed by TN (32.1%). Other subtypes were luminal B (10.1% ) and non-luminal HER2+ (6.3%). Conclusions. The findings of the present study are in line with the literature and should assist in management of breast cancer in our country.
In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.
Dong Joon Park;Sungkyun Park;Seong Won Ma;Hoekyeong Seo;Sang Gil Lee;Kyung-Eun Lee
Annals of Occupational and Environmental Medicine
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v.34
/
pp.5.1-5.10
/
2022
Background: Some epidemiological studies have estimated exposure among flight attendants with and without breast cancer. However, it is difficult to find a quantitative evaluation of occupational exposure factors related to cancer development individually in the case of breast cancer in flight attendants. That is, most, if not all, epidemiological studies of breast cancer in flight attendants with quantitative exposure estimates have estimated exposure in the absence of individual flight history data. Case presentation: A 41-year-old woman visited the hospital due to a left breast mass after a regular check-up. Breast cancer was suspected on ultrasonography. Following core biopsy, she underwent various imaging modalities. She was diagnosed invasive ductal carcinoma of no special type (estrogen receptor positive in 90%, progesterone receptor positive in 3%, human epidermal growth factor receptor 2/neu equivocal) with histologic grade 3 and nuclear grade 3 in the left breast. Neoadjuvant chemotherapy was administered to reduce the tumor size before surgery. However, due to serious chemotherapy side effects, the patient opted for alternative and integrative therapies. She joined the airline in January, 1996. Out of all flights, international flights and night flights accounted for 94.9% and 26.2, respectively. Night flights were conducted at least four times per month. Moreover, based on the virtual computer program CARI-6M, the estimated dose of cosmic radiation exposure was 78.81 mSv. There were no other personal triggers or family history of breast cancer. Conclusions: This case report shows that the potentially causal relationship between occupational harmful factors and the incidence of breast cancer may become more pronounced when night shift workers who work continuously are exposed to cosmic ionizing radiation. Therefore, close attention and efforts are needed to adjust night shift work schedules and regulate cosmic ionizing radiation exposure.
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