Chemopreventive Agent For Breast Cancer Research Articles

Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer (BC) chemoprevention. We evaluated change in a convolutional neural network (CNN)-based BC risk model applied to mammograms among women enrolled in SWOG S0812, which randomized 208 premenopausal high-risk women to receive oral vitamin D3 20,000IU weekly or placebo for 12 months. We applied the CNN model to mammograms collected at baseline (n = 109), 12 months (n = 97) and 24 months (n = 67), and compared changes in CNN risk score between treatment groups. Change in CNN score was neither significantly different between vitamin D and placebo groups at 12 months (0.005 vs. 0.002, p = 0.875) nor at 24 months (0.020 vs. 0.001, p = 0.563). The findings are consistent with the primary analysis of S0812, which did not demonstrate significant changes in MD with vitamin D supplementation compared to placebo. There is an ongoing need to evaluate biomarkers of response to novel BC chemopreventive agents.

Cytotoxic Activity of Cambodian Leaves Extract (Plumeria acuminate) on Breast Cancer Cells and COX-2 Targeted Prediction of Its Chemical Contents

Cambodian leaves are suspected to contain stigma sterol which may target Cyclo-Oxygenase-2 (COX-2) or Estrogen Receptor (ER) to contribute to its cytotoxic activity on breast cancer cells. This study aimed to determine the potential of Cambodian leaf compounds and extracts as chemopreventive agents for luminal breast cancer with a molecular target of COX-2. Ethanol was used to extract the active compound of Cambodian leaves. The study on chemical activity against COX-2 employed molecular docking with Molecular Operating Environment (MOE) and the cytotoxic property of Cambodian leaf extract (CLE) on T47D was determined using the trypan blue exclusion method. The extraction yielded as 4.87% w/w CLE. Thin layer chromatography showed that Cambodian leaves contain sterol. Molecular docking confirmed that several sterol compounds have greater affinity to COX-2 than native ligands indicating that they are potent as COX-2 inhibitors. They are Stigmast-7-en-3-ol, Lupeol Acetate, and Lupeol carboxylic acid with docking scores of -14.3874, -13.8098, and -14.1045 kcal/mol respectively. The CLE exhibited cytotoxic activity on T47D cells with an IC50 value of 18 μg/mL. Therefore, CLE has a potential effect as a chemopreventive agent for breast cancer and potentially as a COX-2 inhibitor.Keywords: Cambodian leaf extract, breast cancer, COX-2 inhibitor, chemopreventive.

Asiaticoside Increases Caspase-9 Activity in MCF-7 Cells and Inhibits TNF-α and IL-6 Expression in Nude Mouse Xenografts via the NF-κB Pathway.

Background: We hypothesized that the antitumor effects of asiaticoside on breast cancer are driven by its ability to decrease the expression of tumor inflammation-promoting genes and increase apoptotic signaling. In this study, we aimed to better understand the mechanisms of action of asiaticoside as a chemical modulator or as a chemopreventive agent in breast cancer. Methods: MCF-7 cells were cultured and treated with 0, 20, 40, and 80 μM asiaticoside for 48 h. Fluorometric caspase-9, apoptosis, and gene expression analyses were conducted. For the xenograft experiments, we divided nude mice into the following 5 groups (10 animals per group): group I, control mice; group II, untreated tumor-bearing nude mice; group III, tumor-bearing nude mice treated with asiaticoside at weeks 1-2 and 4-7 and injected with MCF-7 cells at week 3; group IV, tumor-bearing nude mice injected with MCF-7 cells at week 3 and treated with asiaticoside beginning at week 6; and group V, nude mice treated with asiaticoside, as a drug control. After treatment, weight measurements were performed weekly. Tumor growth was determined and analyzed using histology and DNA and RNA isolation. Results: In MCF-7 cells, we found that asiaticoside increased caspase-9 activity. In the xenograft experiment, we found that TNF-α and IL-6 expression decreased (p < 0.001) via the NF-κB pathway. Conclusion: Overall, our data suggest that asiaticoside produces promising effects on tumor growth, progression, and tumor-associated inflammation in MCF-7 cells as well as a nude mouse MCF-7 tumor xenograft model.

Abstract A003: Identification of a potential chemoprevention agent for BRCA1- mutated cancers

Abstract BRCA1 mutation carriers are predisposed to developing aggressive breast, ovarian, and other cancers at a relatively early age. Unfortunately, these cancers lack an effective chemoprevention option. We have found that cells containing mutant BRCA1 harbor defective repair of oxidative DNA damage, an early trigger to tumorigenesis. Therefore, we sought to target this defect and discover a novel chemoprevention agent for these cancers. High-throughput screening of a chemical library identified a novel class of small-molecules that enhance repair of oxidative DNA damage, which we termed DNA repair-activating agents. One of these agents, benserazide, increased base-excision repair of oxidative DNA damage utilizing a cell-based DNA repair assay, decreased levels of 8-oxo-g (i.e. most common oxidized lesion in human genome) using flow cytometric analysis, and decreased levels of oxidative DNA damage as determined by alkaline comet assay modified for detection of oxidized DNA lesions. These results were observed in mutant but not wild-type BRCA1 breast cancer cells. Benserazide, but not tamoxifen (current FDA-approved breast cancer chemoprevention agent), also decreased in vitro tumorigenesis of mutant BRCA1 or BRCA1-depleted breast cancer cells according to the soft-agar colony formation assay, and delayed tumor formation in vivo using a xenograft mouse model. Lastly, benserazide led to elevated levels of 8-oxo-dG (a by-product of base-excision repair) in conditioned media of mutant BRCA1 breast cancer cells, and concurrently increased serum levels of 8oxodG and decreased tumor burden in mice. Taken together, benserazide is a DNA-repair activating agent that enhances repair of oxidative DNA damage and decreases tumorigenesis in vitro and in vivo, and thus may serve as a potential chemoprevention agent for BRCA1-mutated cancers. Further, circulating levels of 8oxoG/8oxodG may function as a predictive biomarker for the efficacy of benserazide, which would prove useful in the clinical evaluation of benserazide for cancer chemoprevention. Citation Format: Sujeeth Shanmugam, Eboni Hosch, Dipasri Konar, James M. Ford, Elizabeth Alli. Identification of a potential chemoprevention agent for BRCA1- mutated cancers [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A003.

Suppression of Molecular Targets and Antiproliferative Effect of Citronellal on Triple-Negative Breast Cancer Cells.

Triple-Negative Breast Cancer (TNBC) requires targeted therapies to better manage and prevent metastatic mammary gland tumors. Due to the resistance problem associated with the approved drugs, researchers are now focusing on phytochemicals for the treatment of TNBC as they possess pleiotropic mode of action and fewer side effects. To investigate the antiproliferative effect of citronellal on triple-negative breast cancer cells. Anticancer potential of citronellal was explored by employing SRB, MTT, and NRU antiproliferative assay. Further, the effect of citronellal was observed on molecular targets (Tubulin, COX-2, and LOX-5) utilizing in vitro and in silico methods. Furthermore, the efficacy of citronellal was examined on Ehrlich Ascites Carcinoma cells. In addition, the safety profiling of it was observed at 300 and 1000 mg/kg of body weight in mice. Citronellal suppresses the growth of MDA-MB-231 cells by more than 50% in NRU assay and ~41% and 32% in SRB and MTT assay, respectively. Further, citronellal's effect was observed on molecular targets wherein it suppressed LOX-5 activity (IC50 40.63±2.27 μM) and prevented polymerization of microtubule (IC50 63.62 μM). The result was more prominent against LOX-5 as supported by molecular docking interaction studies, but a non-significant effect was observed at the transcriptional level. The efficacy of citronellal was also determined in Ehrlich Ascites Carcinoma (EAC) model, wherein it inhibited the growth of tumor cells (45.97%) at 75 mg/kg of body weight. It was non-toxic up to 1000 mg/kg of body weight in mice and did not cause significant lysis of erythrocytes. These observations could provide experimental support for citronellal to be used as a chemopreventive agent for breast cancer.

Chemopreventive and Anticancer Property of Selenoproteins in Obese Breast Cancer.

Obesity is a significant risk factor for various cancers including breast cancer resulting in an increased risk of recurrence as well as morbidity and mortality. Extensive studies on various pathways have been successful in establishing a biological relationship between obesity and breast cancer. The molecular classification of breast cancer includes five groups each having different responses to treatment. Increased levels of inflammatory cytokines seen in obese conditions drive the pro-proliferative pathways, such as the influx of macrophages, angiogenesis, and antiapoptotic pathways. Increased peripheral aromatization of androgens by aromatase increases the circulating estrogen levels which are also responsible for the association of obesity with breast cancer. Also, increased oxidative stress due to chronic low-grade inflammation in obese women plays an important role in carcinogenesis. Despite the availability of safe and effective treatment options for breast cancer, obese women are at increased risk of adverse outcomes including treatment-related toxicities. In the recent decade, selenium compounds have gained substantial interest as chemopreventive and anticancer agents. The chemical derivatives of selenium include inorganic and organic compounds that exhibit pro-oxidant properties and alter cellular redox homeostasis. They target more than one metabolic pathway by thiol modifications, induction of reactive oxygen species, and chromatin modifications to exert their chemopreventive and anticancer activities. The primary functional effectors of selenium that play a significant role in human homeostasis are selenoproteins like glutathione peroxidase, thioredoxin reductase, iodothyronine deiodinases, and selenoprotein P. Selenoproteins play a significant role in adipose tissue physiology by modulating preadipocyte proliferation and adipogenic differentiation. They correlate negatively with body mass index resulting in increased oxidative stress that may lead to carcinogenesis in obese individuals. Methylseleninic acid effectively suppresses aromatase activation thus reducing the estrogen levels and acting as a breast cancer chemopreventive agent. Adipose-derived inflammatory mediators influence the selenium metabolites and affect the proliferation and metastatic properties of cancer cells. Recently selenium nanoparticles have shown potent anticancer activity which may lead to a major breakthrough in the management of cancers caused due to multiple pathways. In this review, we discuss the possible role of selenoproteins as chemopreventive and an anticancer agent in obese breast cancer.

Study of Selected Flavonoid Structures and Their Potential Activity as Breast Anticancer Agents.

Flavonoids contain pharmacological effects that help to protect cells from damage. However, the anticancer activity of flavonoids is related to their modulation of signal transduction pathways within cancer cells. Natural substances such as flavonoids have immune-stimulating anti-tumor effect that could lower breast cancer risk. However, various diseases included Alzheimer’s and cancer disease are associated with flavonoids intake due to their ability as antioxidant agent to alter essential cellular enzyme’s function. Therefore, through interaction between flavonoids and Cytochrome P450 (CYP) family enzymes led to make them chemopreventive agents for breast cancer. In this analysis, the chemo-informatics properties of 5 selective flavonoid derivatives and their efficiency as anti-breast cancer drugs were evaluated. Flavonoid ligands were docked with the predicted protein, which is human placental aromatase complexes with exemestane, a breast cancer drug (3S7S). Based on various docking energies, the molecular characteristics and bioactivity score of the following components, C15H12O6 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydro-4H-chromen-4-one and C15H12O5 5,8-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one showed greatest molecular properties and bioactivity docking scores of −8.633117 and −8.633117 kcal/mol respectively. Therefore, both compounds could be considered antitumor agent.

Data-Driven identification of chemopreventive agents for breast cancer

Preclinical animal models of breast cancer provide the opportunity to identify chemopreventive drugs with single-agent activity as well as effective multi-modality regimens for primary as well as secondary prevention in high-risk persons. Our group has used the 7,12-dimethylbenz(a)anthracene (DMBA) mouse model of carcinogen-induced breast cancer to explore the clinical potential of two tyrosine kinase inhibitors and a nucleoside analog as chemopreventive agents. All three agents exhibited promising preclinical activity both as monotherapy and as components of combination therapy with the standard chemotherapy drug paclitaxel. The tumors developing despite chemoprevention were not only small and grew slowly, but they also displayed a uniquely more pro-apoptotic protein expression profile. Hence, our experimental chemopreventive drugs were capable of preventing the development of aggressive mammary gland tumors with an apoptosis-resistant protein expression profile.

BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression

The molecular processes by which some human ductal carcinoma in situ (DCIS) lesions advance to the more aggressive form, while others remain indolent, are largely unknown. Experiments utilizing a patient-derived (PDX) DCIS Mouse INtraDuctal (MIND) animal model combined with ChIP-exo and RNA sequencing revealed that the formation of protein complexes between B Cell Lymphoma-9 (BCL9), phosphoserine 727 STAT3 (PS-727-STAT3) and non-STAT3 transcription factors on chromatin enhancers lead to subsequent transcription of key drivers of DCIS malignancy. Downregulation of two such targets, integrin β3 and its associated metalloproteinase, MMP16, resulted in a significant inhibition of DCIS invasive progression. Finally, in vivo targeting of BCL9, using rosemary extract, resulted in significant inhibition of DCIS malignancy in both cell line and PDX DCIS MIND animal models. As such, our studies provide compelling evidence for future testing of rosemary extract as a chemopreventive agent in breast cancer.

Antitumor effects of seleno-β-lactoglobulin on human breast cancer MCF-7 and MDA-MB-231 cells in vitro

Seleno-β-lactoglobulin (Se-β-Lg) was synthesized using seleninic acid, an organoselenium compound, and β-lactoglobulin (β-Lg), an important component of milk. Previously, we have studied the effects of Se-β-Lg on hepatocellular carcinoma and gastric cancer cells. In this study, we investigated the antitumor effects of Se-β-Lg and its potential mechanisms of action against human breast cancer cells (MCF-7 and MDA-MB-231). The results showed that the half-maximal inhibitory concentrations (IC50) of Se-β-Lg were 40.84 μg/mL for MCF-7 cells and 46.04 μg/mL for MDA-MB-231 cells at 24 h, while the compound showed no cytotoxicity to normal breast cells. The involvement of reactive oxygen species (ROS) in the activation of the apoptotic signaling pathway by Se-β-Lg was demonstrated by the incubation of cells with 80 μg/mL Se-β-Lg and determination of the rates of apoptosis and intracellular ROS levels after the addition of 10 mM N-acetyl-l-cysteine, a ROS inhibitor. Our findings revealed highly potent anticancer activities of Se-β-Lg against breast cancer cells and suggested that the compound may be used as a chemopreventive agent for breast cancer. Furthermore, we thoroughly elucidated the antitumor mechanism of Se-β-Lg.

Breast cancer prevention in older women: an algorithm to choose an optimal preventive agent

BackgroundBreast cancer is a significant cause of morbidity and mortality in older women. The current study presents new, comprehensive guidelines for providing chemoprevention to older women.ObjectiveThe objective of this study was to develop and pilot test a chemopreventive choice algorithm to assess its feasibility for older women at high risk of breast cancer.DesignThe study observed outcomes of 23 older adult females being treated with one of the four different chemopreventive agents. A novel algorithm protocol was utilized for individualized chemopreventive selection.SettingThe study was conducted in a high-risk outpatient clinic for older women.ParticipantsOlder outpatient females at high risk (N=23) were offered chemopreventive options based on individual criteria.InterventionLiterature review for breast cancer chemopreventive agents informed our development of a logic-based algorithm to guide treatment protocol and chemopreventive choice optimization. Selective estrogen receptive modulators (SERMs) were avoided in women with endometrial cancer risk (ie, pre-hysterectomy individuals), but used in women with low thromboembolic event (TE) risk. Raloxifene was used with osteoporotic women. Aromatase inhibitors (AIs) were used in women with high TE risk. Women without TE risks are advised to take SERMs. When bone density decreased due to AI use, women were switched to raloxifene.Measurements/resultsOf 23 participants of age ranging from 59 to 80 years (mean=72.6), two women developed estrogen receptor-positive breast cancer. Two participants, one who declined chemoprevention and one treated with an AI, developed breast cancer. All initial chemopreventive agents were selected according to the algorithm. Although minor adverse events occurred, each was managed by discontinuation or replacement of the chemopreventive agent. Discontinuation was most commonly due to side effect concerns or cost rather than experienced side effects.ConclusionOutcomes of the initial utilization of the chemopreventive agent choice algorithm support the viability of the protocol, but further evaluation with a larger and more diverse sample is required.

Non-steroidal anti-inflammatory drug use and breast cancer risk in a prospective cohort study

Introduction In past decades, evidence from both experimental and observational studies has accumulated suggesting that chronic inflammation could promote breast cancer development. Therefore, nonsteroidal anti-inflammatory drugs (NSAIDs), a class of drugs commonly used to treat pain, fever and inflammation, has been proposed as potential chemo-preventive agents for breast cancer. Although inverse associations between NSAIDs and breast cancer risk have been reported in most case-control studies, results from cohort studies are less consistent. Our objective was to assess the association between NSAID use and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self-reported information on NSAID use at baseline has been collected in five EPIC countries (France, Denmark, United Kingdom, the Netherlands and Germany). Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with breast cancer incidence with adjustment for potential confounders. We also assessed effect modification by breast cancer risk factors and examined the associations within specific breast cancer subtypes. Results Among the 140,981 women included in the analysis, 7% were regularly using NSAIDs at baseline. During a median follow-up time period of 13 years, 7379 incident breast cancer cases were diagnosed (816 in situ and 6563 invasive). In multivariable models, there was no statistically significant association between regular NSAID use and breast cancer risk overall. Compared with women who were not regular users at baseline, the HR for regular users of NSAIDs was 0.99 (95% CI = 0.90 to 1.08). Risk estimates did not vary significantly by histological subtypes, by hormone receptor status of the tumor, by breast cancer risk factors or by country (all Pinteraction/heterogeneity between 0.10 and 0.92). However, among postmenopausal women, a statistically significant interaction was observed between NSAID use and ever use of menopausal hormonal therapy (MHT) for invasive breast cancer cases [among MHT ever users: HRNSAID use = 0.84 (0.73–0.96); among MHT never users: HRNSAID use = 1.08 (0.93–1.25); Pinteraction = 0.05], but not for in situ cases [among MHT ever users: HR NSAID use = 1.25 (0.82–1.92); among MHT never users: HR NSAID use = 1.18 (0.81–1.73); Pinteraction = 0.99]. Conclusions and perspectives Our results indicate potential effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in-depth investigation in studies with accurate data on both NSAID and MHT use, including type, dosage, frequency and duration of use. We are currently exploring this further in a study within the French-EPIC cohort (E3 N cohort) including 61,107 women with individual drug-reimbursement data available from years 2004 to 2011, including dose, duration and subtypes of NSAIDs. If the interaction between MHT use, NSAIDs and breast cancer risk is confirmed, this could have public health implications with respect to how MHT is administered.

Wpływ substancji zawartych w pieczarkach na organizm człowieka

Agaricus bisporus (white button mushroom) contains significant amounts of dietary fibers, microelements and other important compounds. While it is often underrated, numerous studies prove its positive impact on health. Several compounds found in Agaricus bisporus provide beneficial effects on diabetic and cardiovascular diseases and may lower blood glucose, cholesterol and LDL. Those mushrooms are also a potential breast cancer chemopreventive agent since they were proven to suppress aromatase and estrogen synthesis. Therefore, it may be useful in estrogen-dependent breast tumors. What is more, white button mushroom contains low amount of fat and is low calorie. It can be effectively used in diets to lower body weight. Also, compounds found in white button mushroom have impact on human immune system. They lead to increase of IgA production and stimulates lymphocytes by increasing levels of interleukin. Therefore, white button mushroom is not only valuable thanks to its taste but also because of its impact on human health. Properly prepared it can be an important ingredient of everyday meals.

Toxicology studies of indole-3-carbinol in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of indole-3-carbinol in Harlan Sprague Dawley rats and B6C3F1/N mice (gavage studies).

Indole-3-carbinol is sold as a sole ingredient in dietary supplements or as a combination nutraceutical along with a variety of herbs and/or vitamins. It is marketed for its potential ability to prevent cancer and provide other health benefits, such as detoxifying the liver and boosting the immune system. Indole-3-carbinol is a naturally formed breakdown product of glucosinolate glucobrassicin, a component found in cruciferous vegetables of the Brassica genus, including broccoli, brussels sprouts, cauliflower, cabbage, kale, kohlrabi, and turnips. Exposure to indole-3-carbinol occurs through the oral route through the ingestion of Brassica vegetables or dietary supplements. Indole-3-carbinol was nominated by the National Cancer Institute for toxicity and carcinogenicity testing because of its occurrence in natural products and for its potential use as a breast cancer chemopreventive agent. Male and female F344/N rats and Harlan Sprague Dawley rats received indole-3-carbinol in corn oil by gavage for 3 months or 2 years, respectively. Male and female B6C3F1/N mice received indole-3-carbinol in corn oil gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli, rat bone marrow cells, and mouse peripheral blood erythrocytes. (Abstract Abridged).

Cell cycle and apoptosis pathway modulation by Tualang honey in ER-dependent and -independent breast cancer cell lines

We previously demonstrated that Tualang honey (TH) induced apoptosis in breast cancer cell lines, via activation of caspase-3/7, -8, and -9 and mitochondrial membrane depolarization. Here we investigated the effect of TH on cell cycle progression and its regulatory molecules as well as apoptosis-related signaling molecules in estrogen receptor-dependent MCF-7 and -independent breast MDA-MB-231 cancer cells. Flow cytometry analysis shows that 24 h treatment with 1% TH caused G2/M phase arrest in MCF-7 but S phase arrest in MDA-MB-231 cells. Significant changes in the expression of apoptosis-related genes were observed in MCF-7 cells but not in MDA-MB-231 cells. We further demonstrated by Western blotting that TH increased the expression of p53, p21, and FADD proteins in MCF-7 cells and TRADD, FADD, and p21 proteins in MDA-MB-231 cells. This study shows that TH differentially affects the cell cycle progression of MCF-7 and MDA-MB-231 cells via p53-dependent and -independent p21 signaling, respectively, and apoptosis via the death receptor pathway is indicated. Taken together, the ability of TH to modulate cell signaling pathways suggest the potential value of a readily consumed honey as a chemopreventive agent for breast cancer.

A synthetic chalcone, 2'-hydroxy-2,3,5'-trimethoxychalcone triggers unfolded protein response-mediated apoptosis in breast cancer cells

The primary aim of this study was to find novel chemopreventive agents effective against breast cancer. Endoplasmic reticulum (ER) stress can induce apoptosis through the unfolded protein response (UPR). 2'-Hydroxy-2,3,5'-trimethoxychalcone (DK143) is a synthetic flavonoid derivative. The present study provides evidence supporting the role of the UPR in mediating the apoptotic effect of DK143. Treatment with DK143 triggered apoptosis through the activation of the caspase pathway in MDA-MB-231 breast cancer cells without affecting viability of MCF10A non-transformed breast epithelial cells. Further analysis revealed that DK143 produced reactive oxygen species (ROS) in MDA-MB-231 cells, but not in MCF10A cells, and upregulated the expression of ER stress sensors, including GRP78/BiP, IRE1α, CHOP, and Bim in MDA-MB-231 cells. In addition, UPR-related transcription factors, XBP-1 and CHOP, were activated by DK143. Moreover, silencing of IRE1α or CHOP by corresponding siRNA molecules attenuated DK143-induced apoptosis. Furthermore, DK143 suppressed mouse tumor growth in vivo. These results demonstrate that promoting ER stress in breast cancer cells via UPR induction might be a promising strategy for developing new chemotherapeutic or chemopreventive agents for breast cancer.

Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach.

Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.

Vasomotor symptoms, BMI, and adherence to tamoxifen in the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial (P-1).

1501 Background: Tamoxifen (T) is underutilized as a chemopreventive agent for breast cancer (BC), despite a 50% reduced risk of developing breast cancer in high risk women with use of T vs. placeb...

Punica granatum and its therapeutic implications on breast carcinogenesis: A review.

Punica granatum has a recorded history of pharmacological properties which can be attributed to its rich reservoir of phytochemicals. Investigations in recent years have established its tremendous potential as an antitumorogenic agent against various cancers including breast cancer, which is the second leading cause of cancer-related deaths in women. The plausible role of Punica as a therapeutic agent, as an adjuvant in chemotherapy, and its dietary implications as chemopreventive agent in breast cancer have been explored. Mechanistic studies have revealed that Punica extracts and its components, individually or in combination, can modulate and target key proteins and genes involved in breast cancer. Our earlier finding also demonstrated the role of methanolic extract of pomegranate pericarp in reducing proliferation in breast cancer by binding to estrogen receptor at the same time not affecting uterine weight unlike estradiol or tamoxifen. This review analyses other plausible mechanisms of Punica in preventing the progression of breast cancer and how it can possibly be a therapeutic agent by acting at various steps of carcinogenesis including proliferation, invasion, migration, metastasis, angiogenesis, and inflammation via various molecular mechanisms.

Soy and Breast Cancer, have we Analyzed all the Risks?

In the United States women have a 1 in 8 lifetime risk for developing breast cancer leading women to turn to natural products for breast cancer prevention. One natural product women have turned to for breast cancer prevention is soy which has been extensively studied for its health benefits. Soy has been classified as a phytoestrogen and as such has been studied as a chemopreventive agent in breast cancer. Results from preclinical and epidemiological studies involving soy have been contradictory. In part, the contradictory results may stem from study design and dietary sources of soy studied. In the US exposure to soy is primarily unfermented soy, but most epidemiological studies reporting breast cancer chemopreventive effects of soy involve fermented soy exposure. Thus, a direct comparison of the effects of unfermented and fermented soy on breast cancer in Western women is warranted.