Tamoxifen resistance is often observed in the majority of estrogen receptor-positive breast cancers and it remains as a serious clinical problem cancer management. Increased aerobic glycolysis has been proposed one mechanisms for acquired to chemotherapeutic agents cells such adriamycin. Herein, we report that rates LCC2 LCC9--tamoxifen-resistant human cell lines derived from MCF7--are higher than those MCF7S, which parent MCF7 subline. Inhibition key glycolytic enzyme hexokinase-2 resulted...

Oxidative stress after stroke is associated with the inflammatory system activation in brain. The complement cascade, especially degradation products of component 3, a key mediator cerebral ischemia. We have shown that pro-inflammatory 3 increased by oxidative ischemic mice using DNA array. In this study, we investigated whether up-regulation directly related to transient focal ischemia and oxygen-glucose deprivation brain cells. Persistent expression was reduced copper/zinc-superoxide...

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, has been reported to be immunotoxic agrochemical compound. was shown decrease the number of macrophages rats suppress monocyte phagocytic activity mice. However, effect on macrophage cell viability remains unclear. this study, we evaluated cytotoxic mouse line, RAW264.7 its possible...

Mitochondria are essential organelles that produce ATP and regulate cell growth, proliferation, death. To maintain homeostasis, fusion fission of mitochondria must be strictly regulated. Even though oligomerization synthase could affect the mitochondrial morphology, exact mechanism is not clear. We confirmed structure function ATP5B, which a major component catalytic center complexes, closely connected to morphology. ATP5B itself can enhance elongation mitochondria. Moreover, mutations...

The risk factors for women developing breast and endometrium cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy (ERT) in particular has been correlated slight increased cancer risk, although the numerous benefits ERT may negate this harmful side effect. Equilenin equilin equine estrogens which make up between 30% 45% most widely prescribed formulation, Premarin (Wyeth-Ayerst). In study we have synthesized catechol metabolites equilenin...

The inactivation mechanism(s) of human glutathione S-transferase P1-1 (hGST P1-1) by the catechol metabolite Premarin estrogens, 4-hydroxyequilenin (4-OHEN), was (were) studied means site-directed mutagenesis, electrospray ionization mass spectrometric analysis, titration free thiol groups, kinetic studies irreversible inhibition, and analysis band patterns on nonreducing sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE). four cysteines (Cys 14, Cys 47, 101, 169 in...

Peroxiredoxin 5 (Prx5) is a member of family consisting six antioxidant enzymes. Prx5 ubiquitously expressed in various tissues including mitochondria and peroxisomes, implying that functions as regulator the cellular oxidation state. plays critical role protecting cells from oxidative stress by inhibiting accumulation reactive oxygen species cell death. Overexpression mammary tissue associated with poor prognosis breast cancer. The present study was conducted to elucidate regulatory...

Equilenin, an important component of a widely prescribed hormone replacement formualtion for postmenopausal women, is metabolized by mammalian P450 enzymes to the catechol 4-hydroxyequilenin (4-OHEN). The oxidized o-quinone derivative 4-OHEN known form cyclic covalent adducts with DNA [Bolton, J. (1998) Chem. Res. Toxicol. 11, 1113] in vitro and vivo. characteristics 4-OHEN−DNA adduct formation were investigated oligonucleotides 5'-d(CCATCGCTACC) (I), its complementary strand...

Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, on development and recurrence hepatocellular carcinoma (HCC) were investigated using diethylnitrosamine (DEN)‑induced rat model HCC. Tumor foci characterized by gross examination histopathological characteristics, including proliferation, hepatic progenitor cell content expression hepatocarcinoma‑specific molecular markers. Potential target molecules to determine...

The biguanide drug metformin has been widely used for the treatment of type 2 diabetes, and there is evidence supporting anticancer effect despite some controversy. Here, we report growth inhibitory activity in breast cancer (MCF-7) cells, both vitro vivo, associated metabolic changes. In particular, a decrease well-known oncometabolite 2-hydroxyglutarate (2-HG) was discovered by metabolomics approach. 2-HG accompanied reduction histone methylation, consistent with known tumorigenic...

Phytoestrogens are selective estrogen receptor modulators (SERMs) with potential for use in hormone replacement therapy (HRT) to relieve peri/postmenopausal symptoms. This study was aimed at elucidating the molecular mechanisms underlying SERM properties of extract Korean-grown Opuntia ficus-indica (KOFI). The KOFI induced response element (ERE)-driven transcription breast and endometrial cancer cell lines expression endogenous estrogen-responsive genes cells. flavonoid content different...

Larrea nitida Cav. (LNC), which belongs to the family Zygophyllaceae, is widely indigenous and used in South America treat various pathological conditions. It contains antioxidant antiinflammatory but toxic nordihydroguaiaretic acid (NDGA) as well O ‐methylated metabolite of NDGA (MNDGA) bioactive compounds. The hepatic metabolism‐based toxicological potential extracts LNC (LNE), NDGA, MNDGA has not previously been reported. present study aimed characterize phase I II metabolism reactive...

Spent coffee grounds (SCG) are the most abundant byproduct and generally discarded as waste. The horticultural use of SCG compost (SCGC) has become popular due to a growing interest in environmentally friendly measures for waste disposal. Estrogen-like endocrine disrupting chemicals soil can be absorbed by plants subsequently humans who consume these plants. objectives this study determine phytochemical profiles extracts SCGC evaluate estrogen-like activities SCG, SCGC, major phenolic acids,...

Redox and/or electrophilic metabolites formed during estrogen metabolism may play a role in carcinogenesis. 4-Hydroxyequilenin (4-OHEN) is the major phase I catechol metabolite of equine estrogens equilenin and equilin, which are components most widely prescribed replacement formulation, Premarin. Previously, we have found that 4-OHEN rapidly autoxidized to an o-quinone vitro caused toxic effects such as inactivation human detoxification enzymes. has also been shown be substrate for...

Glutathione S-transferases (GSTs) are a family of detoxification isozymes that protect cells by conjugating GSH to variety toxic compounds, and they may also play role in the regulation both cellular proliferation apoptosis. We have previously shown human GST P1-1, which is most widely distributed extrahepatic isozyme, could be inactivated catechol estrogen metabolite 4-hydroxyequilenin (4-OHEN) vitro [Chang, M., Shin, Y. G., van Breemen, R. B., Blond, S. Y., Bolton, J. L. (2001)...

4-Methoxyequilenin (4-MeOEN) is an O-methylated metabolite in equine estrogen metabolism. O-methylation of catechol estrogens considered as a protective mechanism; however, comparison the properties 4-MeOEN with estradiol (E2) human breast cancer cells showed that proliferative, estrogenic agent may contribute to carcinogenesis. results from 4-hydroxyequilenin, major present hormone replacement therapeutics, which causes DNA damage via quinone formation, raising possibility synergistic...

Sakuranetin (SKN), found in cherry trees and rice, is a flavanone with various pharmacological activities. It biosynthesized from naringenin rice or trees, the metabolism of SKN has been studied non-human species. The present study aimed to investigate metabolic pathways human liver microsomes identify phase I II metabolites, as well evaluate potential for drug⁻herb interactions through modulation drug metabolizing enzymes (DMEs). HPLC-DAD HPLC-electrospray mass spectrometry were used...

Opuntia ficus indica (OFI) is grown abundantly in arid areas and its fruits are regarded as an important food nutrient source owing to the presence of flavonoids, minerals, proteins. The previous report that OFI exerts phytoestrogenic activity makes it plausible for OFI-containing supplements be used alternative estrogen replacement therapy. In case polypharmacy with consumption botanicals post- or peri-menopausal women, critical determine potential drug-OFI interaction due modulation drug...