Cell adhesion proteins altered by 17β estradiol and parathion in breast epithelial cells

Echiburú-Chau²,

Roy³

et al. 2011

Oncol Rep

Abstract. Curcumin (diferuloylmethane) is a well known antioxidant that exerts anti-proliferative and apoptotic effects. The effects of curcumin were evaluated in a breast cancer model that was developed with the immortalized breast epithelial cell line, MCF-10F after exposure to low doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation, and subsequently cultured in the presence of 17β-estradiol (estrogen). This model consisted of human breast epithelial cells in different stages of transformation: i) a control cell line, MCF-10F, ii) an estrogen-treated cell line, named Estrogen, iii) a malignant cell line, named Alpha3 and iv) a malignant and tumorigenic, cell line named Alpha5. Curcumin decreased the formation of hydrogen peroxide in the control MCF-10F, Estrogen and Alpha5 cell lines in comparison to their counterparts. Curcumin had little effect on NFκB (50 kDa) but decreased the protein expression in the Estrogen cell line in comparison to their counterparts. Curcumin enhanced manganese superoxide dismutase (MnSOD) protein expression in the MCF-10F and Alpha3 cell lines. Results indicated that catalase protein expression increased in curcumin treatedAlpha3 and Alpha5 cell lines. Curcumin slightly decreased lipid peroxidation in the MCF-10F cell lines, but significantly (P<0.05) decreased it in the Alpha5 cell line treated with curcumin in comparison to their counterparts as demonstrated by the 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) levels. It can be concluded that curcumin acted upon oxidative stress in human breast epithelial cells transformed by the effect of radiation in the presence of estrogen. IntroductionOxidative stress is one of the important pathogenic factors of cancer development. Among the antioxidants, curcumin(1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione; diferuloylmethane) is a well-known major dietary natural yellow pigment derived from the rhizome of the herb Curcuma longa (Zingiberaceae). It is also named turmeric and is a perennial herb belonging to the ginger family, native to India and Southeast Asia. It has been shown to be a potent anti-inflammatory, antioxidant, anticarcinogenic and chemopreventive agent (1,2). This phytochemical has also been shown to suppress the proliferation of numerous types of tumor cells (3-6). Curcumin has been previously shown to prevent the formation of many chemically-induced cancers including mammary cancer in mice (7-9).Under oxidative stress conditions, superoxide anions are produced which are converted to hydrogen peroxide through a specific antioxidant system, and then to water to complete the detoxification pathway (10,11). The hydrogen peroxide formation favors others reactive oxygen species (ROS) formation and an increase of this molecules may play an important role in carcinogenesis (12).It is known that curcumin interferes with the transcription activation induced by transcription factors, such as nuclear factor-κB (NFκB) resulting in the negative regulation of various cell cycle control genes and onc...

“…Protein expression was evaluated by peroxidase immunochemical staining (37,38). The cells were plated on a 4-well glass chamber slide (Nunc, Inc., Naperville, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

Protective role of curcumin in oxidative stress of breast cells

Echiburú-Chau²,

Roy³

et al. 2011

Oncol Rep

“…The genes and protein expression alterations we found induced by pa rathion alone or in combination with 17β-estradiol in cultured breast epithelial cells (44) induced malignant transformation of MCF-10F confirmed by anchorage-independency and invasive capabilities. Parathion alone efficiently elevated the expression of EGFR, c-kit, Trio, Rac 3, Rho-A, and mutant p53 proteins.…”

Section: Discussionmentioning

confidence: 95%

Catechol estrogens as biomarkers for mammary gland cancer

2011

Int J Oncol

Abstract. The origin of human tumors has been attributed to the exposure to several environmental chemicals and implicated in the increase of incidence in breast cancer. Progression of breast cancer follows a complex multistep process that seems to depend on various exogenous and endogenous factors. The aim of this study was to examine the effects of the organophosphorous pesticide malathion in the presence of estrogen on neoplastic transformation of rat mammary glands. Virgin female rats were sacrificed after 30, 124 and 240 days of 5-day injections twice a day. There were four groups: i) control, ii) malathion (22 mg/100 g body weight, BW), iii) 17β-estradiol (30 µg/100 g BW) and iv) combination of both. Progressive alterations in ducts were observed by the effect of malathion in comparison to control after 240 days. Ducts markedly increased in size and number of cells per square millimeter and tumors similar to ductal carcinoma were originated. The increase in number of proliferative ducts per square millimeter was significantly (P<0.05) higher in malathion-treated animals compared to the other groups. Progressive alterations in lobules with estrogen treatment were found after 240 days. Lobules became markedly abnormal, referred to as secretory lobules, increased in number and size and the tumors originated were similar to lobular carcinoma. The increase in number of secretory lobules was significantly (P<0.05) higher in estrogentreated animals compared to the other groups. Treatment with the combination of malathion and estrogen gave rise to tumors constituted of both proliferative ducts and secretory lobules as well as formation of estrogen metabolites such as 2 and 4 catechol estrogens in the blood of the animals after 240 days. We concluded that morphological changes and alterations in the blood of the animals can be used as biomarkers for mammary gland cancer.

“…Pesticides are currently used to improve agricultural production (5-8). However, insecticides have been classified as carcinogens by the International Agency for Research on Cancer in humans (33)(34)(35). The human data are limited due to the restricted number of studies examining individual pesticides.…”

Section: Discussionmentioning

confidence: 99%

“…However, the human population is exposed not only to pesticides but also to a mixture of estrogenic or estrogen-like agents. Epidemiological and experimental evidence has implicated estrogens in the etiology of breast cancer (33)(34)(35). It is known that estrogens are associated with carcinogenic events in both humans and animals (36,37).…”

Section: Discussionmentioning

confidence: 99%

Human drug metabolism genes in parathion-and estrogen-treated breast cells

Roy²

2007

Int J Mol Med

Self Cite

Abstract. Environmental chemicals may be involved in the etiology of breast cancer. Among them, organophosphorous compounds are the most widely used pesticides because of their extensive use in agriculture, medicine and industry. The risk of breast cancer is associated with prolonged exposure to female hormones and is attributed to estrogen since prolonged stimulation by steroid hormones may increase cell division. The aim of the present study was to identify the differentially expressed genes encoding enzymes that are important to drug transport and metabolism in parathion-and estrogen-treated human breast epithelial cell lines using cDNA microarrays. MCF-l0F, an immortalized human breast epithelial cell line was treated with parathion and estrogen, either alone or in combination, and malignant cells were developed through a series of sequential steps. Differential expression from the drug metabolism gene array showed that 17 genes were found to be altered either by parathion or estrogen alone, or the combination of both. Among the genes altered by parathion in comparison to the control were CHST5, CHST6 and CHST7 (sulfotransferases); CYP2F1, CYP3A7 and CYP4F3 (CYPs); GSTP1, GSTT2 and MGST1 (GSTs); MT1X (metallothionein); TPMT (methyltransferase); UGT1A1 and UGT2B (UDP glycosyltransferases). The same genes were down-regulated in estrogen alone including several metallothioneins (MT1A, MT1E, MT1H, MT1L and MT2A). The combination of parathion and estrogen induced downregulation of three sulfotransferases, CYP2F1 and CYP4F3, MGST1, all metallothioneins and TPMT genes. There was no change in CYP3A7, GSTP1, GSTT2, UGT1A1 and UGT2B genes in the presence of both substances. It can be concluded from this study that organophosphorous pesticides such as parathion in the presence of estradiol induced changes in human drug metabolism gene expression in breast cells.