Breast cancer is one of the leading causes of mortality among women worldwide due to aggressive behavior, early metastasis, resistance to existing chemotherapeutic agent and high mortality rate. ...Doxorubicin (Dox) is a powerful anti-tumoral drug. It is one of the most active agents for treatment of breast cancer. The aim of the present study was to evaluate the influence of Dox in apoptosis and oxidative stress in the breast cancer cell lines MCF-10F, MCF-7 and MDA-MB-231. These studies showed that Dox decreased anti-apoptotic Bcl-2 protein expression and affected oxidative stress by increasing hydrogen peroxide production and simultaneously decreasing NF-κB gene and protein expression in MCF-7, a tumorigenic triple-positive cell line. Results also indicated that Dox induced apoptosis by upregulating Bax, caspase-8 and caspase-3 and downregulation of Bcl-2 protein expression. On the contrary, ROS damage decreased by increasing SOD2 gene and protein expression and hydrogen peroxide production with parallel NF-κB protein expression decrease in MDA-MB-231, a tumorigenic triple-negative breast cancer cell line. It can be concluded that Dox activated apoptosis by inducing proteolytic processing of Bcl-2 family, caspases and simultaneously decreased oxidative stress by influencing ROS damage in MCF-7 and MDA-MB-231 cell lines.
Breast cancer is the leading cause of cancer-related death in women worldwide. Several studies have addressed the association between cancer in humans and agricultural pesticide exposure. Evidence ...indicates that exposure to organophosphorous pesticides such as parathion and malathion occurs as a result of occupational factors since they are extensively used to control insects. On the other hand, estrogens have been considered beneficial to the organism; however, epidemiological studies have pointed out an increased breast cancer risk in both humans and animals. Experimental female rat mammary gland cancer models were developed after exposure to parathion, malathion, eserine, an acetylcholinesterase inhibitor, and estrogen allowing the analysis of the signs of carcinogenicity as alteration of cell proliferation, receptor expression, genomic instability, and cell metabolism in vivo and in vitro. Thus, pesticides increased proliferative ducts followed by ductal carcinoma; and 17β-estradiol increased proliferative lobules followed by lobular carcinomas. The combination of both pesticides and either eserine or estrogen induced tumors with both types of structures followed by mammary gland tumors and metastasis to the lung and kidneys after 240 days of a 5-day treatment. Studies also showed that these pesticides and eserine decreased three to five times the acetylcholinesterase activity in the serum compared to controls whereas terminal end buds increased in number, being inhibited by atropine. Genomic instability was analyzed in such tissues (mp53, CYP1A2, c-myc, c-fos, ERα, M2R) and pesticides increased protein expression that was stimulated by estrogens but inhibited by atropine. Eserine also transformed the epithelium of the rat mammary gland in the presence of estrogen and increased the number of terminal end buds after treatment inducing mammary carcinomas. Then, enzymatic digestion of such structures gave rise to cells with increased DNA synthesis and induced anchorage independence. Thus, there were changes in the epithelium of the mammary gland influencing breast carcinogenesis. Furthermore, these substances and acetylcholine also showed the signs of carcinogenicity in vitro as cell proliferation, receptor expression (ERα, ErbB2, M2R), genomic instability (c-myc, mp53, ERα, M2R), and cell metabolism. A unique cellular model is also presented here based on the use of MCF-10 F, a non-tumorigenic cell line that represents a valuable clinically translatable experimental approach that identifies mechanistic links for pesticides and estrogen as suspect human carcinogenic agents.
Breast cancer is one of the major health issues confronting women; however, treatment with conventional chemotherapeutic drugs is limited. Currently, paclitaxel is used as a therapeutic clinical ...agent to treat breast cancer that exerts antitumor activity in numerous types of cancer cell. Curcumin (diferuloylmethane), a polyphenol derived from turmeric (Curcuma longa), possesses several properties that could enable it to exert an anticancer effect. Previous reports have demonstrated the synergistic effects of several chemotherapeutic drugs in combination with curcumin. Therefore, the aim of the current study was to evaluate cell death induced by curcumin and paclitaxel alone and in combination in human breast cancer cell lines: MCF7, an epithelial and luminal-like adenocarcinoma cell line triple positive for estrogen and progesterone receptor, and MDA-MB-234, a metastatic human breast cancer cell line triple negative for such receptors, as well as MCF-10F as a normal breast cell line. The results indicated that curcumin and paclitaxel induced apoptosis and necrosis, which was demonstrated through multiple methods, including assays of caspase-3/7 activity, Annexin V, poly(ADP-ribose) polymerase-1 activation and protein expression of caspase-3, nuclear factor (NF)-κB transcription factor and proliferating cell nuclear antigen. The results identified that the combination of curcumin and paclitaxel had a decreased effect on apoptosis in the malignant MDA-MB-231 cell line compared with in MCF7 or MCF-10F. It was demonstrated that the combined treatment with curcumin and paclitaxel resulted in a higher level of apoptosis compared with either substance alone in breast cancer cell lines. Therefore, breast cancer treatment may benefit from the use of a combination of drugs in chemotherapy.
Global cancer burden increased to 14.1 million new cases in 2012; and breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. Curcumin is the ...major bioactive ingredient extracted from the rhizome of the plant Curcuma longa (turmeric). Paclitaxel is a microtubule-stabilizing agent originally isolated from the bark of Taxus brevifolia. Curcumin and paclitaxel were evaluated with two human breast cancer cell lines as the luminal MCF-7 and the basal-like MDA-MB-231 that are either positive or negative for hormonal receptors estrogen receptor, progesterone receptor and HER2, respectively. Results indicated that curcumin combined with paclitaxel decreased c-Ha-Ras, Rho-A, p53 and Bcl-xL gene expression in comparison to control and substances alone in MCF-7 cell line. These two substances alone and combined decreased gene expression of Bcl-2 and NF-κB. However, CCND1 increased when both substances were combined in MCF-7 cells. Such substances decreased Bcl-2 and increased Bax protein expression. However, curcumin alone decreased IκBα and Stat-3 gene expression. Paclitaxel alone and combined increased IκBα and Stat-3. Curcumin alone and combined with paclitaxel increased p53, Bid, caspase-3, caspase-8 and Bax gene expression in MDA-MB-231, whereas Bcl-xL decreased such expression in MDA-MB-231 cells. When paclitaxel and curcumin were combined the expression of Bcl-2 protein was decreased. However, either substance alone and combined increased Bax protein expression corroborating the apoptotic effect of these substances. It can be concluded that curcumin may be of considerable value in synergistic therapy of breast cancer reducing the associated toxicity with use of drugs.
Curcumin (diferuloyl methane) is an antioxidant that exerts antiproliferative and apoptotic effects and has anti-invasive and anti-metastatic properties. Evidence strongly implicates that ...epithelial-mesenchymal transition (EMT) is involved in malignant progression affecting genes such as Slug, AXL and Twist1. These genes are abnormally expressed in many tumors and favor metastasis. The purpose of this study was to determine the potential effect of curcumin on EMT, migration and invasion. Triple-positive and triple-negative breast cancer cell lines for estrogen receptor (ER), progesterone receptor (PgR) and HER/neu were used: i) MCF-10F, a normal immortalized breast epithelial cell line (negative), ii) Tumor2, a malignant and tumorigenic cell line (positive) derived from Alpha5 cell line injected into the immunologically depressed mice and transformed by 60/60 cGy doses of high LET (linear energy transfer) α particles (150 keV/μm) of radiation and estrogen, and iii) a commercially available MDA-MB-231 (negative). The effect of curcumin (30 μM for 48 h) was evaluated on expression of EMT-related genes by RT-qPCR. Results showed that curcumin decreased E-cadherin, N-cadherin, β-catenin, Slug, AXL, Twist1, Vimentin and Fibronectin protein expression, independently of the positivity of the markers in the cell lines. Curcumin also decreased migration and invasive capabilities in comparison to their own controls. It can be concluded that curcumin influenced biochemical changes associated with EMT-related genes that seems to promote such transition and are at the core of several signaling pathways that mediate the transition. Thus, it can be suggested that curcumin is able to prevent or delay cancer progression through the interruption of this process.
Glyphosate is a large-spectrum herbicide that was introduced on the market in 1974. Due to its important impact on the crop industry, it has been significantly diversified and expanded being ...considered the most successful herbicide in history. Currently, its massive use has led to a wide environmental diffusion and its human consumption through food products has made possible to detect it in urine, serum, and breast milk samples. Nevertheless, recent studies have questioned its safety and international agencies have conflicting opinions about its effects on human health, mainly as an endocrine-disrupting chemical (EDC) and its carcinogenic capacity. Here, we conduct a comprehensive review where we describe the most important findings of the glyphosate effects in the endocrine system and asses the mechanistic evidence to classify it as an EDC. We use as guideline the ten key characteristics (KCs) of EDC proposed in the expert consensus statement published in 2020 (La Merrill et al., 2020) and discuss the scopes of some epidemiological studies for the evaluation of glyphosate as possible EDC. We conclude that glyphosate satisfies at least 8 KCs of an EDC, however, prospective cohort studies are still needed to elucidate the real effects in the human endocrine system.
•Glyphosate is the active component of the most commonly used herbicide in the world.•There is conflicting evidence regarding the effects of glyphosate in the endocrine system.•This is the first review that consolidates the mechanistic evidence on glyphosate as endocrine-disrupting chemical (EDC).•Glyphosate satisfies at least 8 key characteristics of an EDC.•Prospective cohort studies are needed in order to elucidate whether glyphosate is an EDC.
Environmental endocrine disruptor chemicals are substances that can alter the homeostasis of the endocrine system in living organisms. They can be released from several products used in daily ...activities. Once in the organism, they can disrupt the endocrine function by mimicking or blocking naturally occurring hormones due to their similar chemical structure. This endocrine disruption is the most important cause of the well‑known hormone‑associate types of cancer. Additionally, it is decisive to determine the susceptibility of each organ to these compounds. Therefore, the present review aimed to summarize the effect of different environmental substances such as bisphenol A, dichlorodiphenyltrichloroethane and polychlorinated biphenyls in both the mammary and the prostate tissues. These organs were chosen due to their association with the hormonal system and their common features in carcinogenic mechanisms. Outcomes derived from the present review may provide evidence that should be considered in future debates regarding the effects of endocrine disruptors on carcinogenesis.
Breast cancer (BC) is the most common cancer among women worldwide.
are responsible for 16-20% of the risk for hereditary BC. Other susceptibility genes have been identified; Fanconi Anemia ...Complementation Group M (
) being one of these. Two variants in
rs144567652 and rs147021911, are associated with BC risk. These variants have been described in Finland, Italy, France, Spain, Germany, Australia, the United States, Sweden, Finnish, and the Netherlands, but not in the South American populations. Our study evaluated the association of the SNPs rs144567652 and rs147021911 with BC risk in non-carriers of
mutations from a South American population. The SNPs were genotyped in 492
-negative BC cases and 673 controls. Our data do not support an association between
rs147021911 and rs144567652 SNPs and BC risk. Nevertheless, two BC cases, one with a family history of BC and the other with sporadic early-onset BC, were C/T heterozygotes for rs144567652. In conclusion, this is the first study related contribution of
mutations and BC risk in a South American population. Nevertheless, more studies are necessary to evaluate if rs144567652 could be responsible for familial BC in
-negatives and for early-onset non-familial BC in Chilean BC cases.
Breast, cervical and ovarian cancers are highly prevalent in women worldwide. Environmental, hormonal and viral-related factors are especially relevant in the development of these tumors. These ...factors are strongly related to oxidative stress (OS) through the generation of reactive oxygen species (ROS). The OS is caused by an imbalance in the redox status of the organism and is literally defined as "an imbalance between ROS generation and its detoxification by biological system leading to impairment of damage repair by cell/tissue". The multistep progression of cancer suggests that OS is involved in cancer initiation, promotion and progression. In this review, we described the role of OS and the interplay with environmental, host and viral factors related to breast, cervical and ovarian cancers initiation, promotion and progression. In addition, the role of the natural antioxidant compound curcumin and other compounds for breast, cervical and ovarian cancers prevention/treatment is discussed.
Cancer development is a multistep process that may be induced by a variety of compounds. Environmental substances, such as pesticides, have been associated with different human diseases. ...Organophosphorus pesticides (OPs) are among the most commonly used insecticides. Despite the fact that organophosphorus has been associated with an increased risk of cancer, particularly hormone‑mediated cancer, few prospective studies have examined the use of individual insecticides. Reported results have demonstrated that OPs and estrogen induce a cascade of events indicative of the transformation of human breast epithelial cells.
studies analyzing an immortalized non‑tumorigenic human breast epithelial cell line may provide us with an approach to analyzing cell transformation under the effects of OPs in the presence of estrogen. The results suggested hormone‑mediated effects of these insecticides on the risk of cancer among women. It can be concluded that, through experimental models, the initiation of cancer can be studied by analyzing the steps that transform normal breast cells to malignant ones through certain substances, such as pesticides and estrogen. Such substances cause genomic instability, and therefore tumor formation in the animal, and signs of carcinogenesis
. Cancer initiation has been associated with an increase in genomic instability, indicated by the inactivation of tumor‑suppressor genes and activation of oncogenes in the presence of malathion, parathion, and estrogen. In the present study, a comprehensive summary of the impact of OPs in human and rat breast cancer, specifically their effects on the cell cycle, signaling pathways linked to epidermal growth factor, drug metabolism, and genomic instability in an MCF‑10F estrogen receptor‑negative breast cell line is provided.
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