Cadmium-stimulated invasion of rat liver cells during malignant transformation: Evidence of the involvement of oxidative stress/TET1-sensitive machinery.

Cadmium (Cd) is recognized as a highly toxic heavy metal for humans in part because it is a multi-organ carcinogen. To clarify the mechanism of Cd carcinogenicity, we have established an experimental system using rat liver TRL1215 cells exposed to 2.5 μM Cd for 10 weeks and then cultured in Cd-free medium for an additional 4 weeks (total 14 weeks).

Products of Oxidative Guanine Damage Form Base Pairs with Guanine.

Among the natural bases, guanine is the most oxidizable base. The damage caused by oxidation of guanine, commonly referred to as oxidative guanine damage, results in the formation of several products, including 2,5-diamino-4-imidazol-4-one (Iz), 2,2,4-triamino-5(2)-oxazolone (Oz), guanidinoformimine (Gf), guanidinohydantoin/iminoallantoin (Gh/Ia), spiroiminodihydantoin (Sp), 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), urea (Ua), 5-guanidino-4-nitroimidazole (NI), spirodi(iminohydantoin) (5-Si and 8-Si), triazine, the M+7 product, other products by peroxynitrite, alkylated guanines, and 8,5'-cyclo-2'-deoxyguanosine (cG). Herein, we summarize the present knowledge about base pairs containing the products of oxidative guanine damage and guanine.

Fatty acid 2-hydroxylase (FA2H) as a stimulatory molecule responsible for breast cancer cell migration.

The functional role of fatty acid 2-hydroxylase (FA2H) is controversial in the field of cancer biology due to the dual role of FA2H, particularly related to its interaction with triple-negative breast cancer (TNBC). A previous biochemical- and clinical-focused study suggested that FA2H could dampen TNBC aggressiveness. However, another epidemiological study demonstrated that FA2H expression is associated with shorter disease-free survival in TNBC cases.

Cannabidiolic acid dampens the expression of cyclooxygenase-2 in MDA-MB-231 breast cancer cells: Possible implication of the peroxisome proliferator-activated receptor β/δ abrogation.

A growing body of experimental evidence strongly suggests that cannabidiolic acid (CBDA), a major component of the fiber-type cannabis plant, exerts a variety of biological activities. We have reported that CBDA can abrogate cyclooxygenase-2 (COX-2) expression and its enzymatic activity. It is established that aberrant expression of COX-2 correlates with the degree of malignancy in breast cancer.

Metalloestrogenic effects of cadmium are absent in long-term estrogen-deprived MCF-7 cells: Evidence for the involvement of constitutively activated estrogen receptor α and very low expression of G protein-coupled estrogen receptor 1.

Cadmium (Cd) has estrogen-like activities in breast cancer; it acts as a metalloestrogen in humans. Prospective cohort studies of Cd and breast cancer risk suggest a significant relationship between increased Cd intake and cancer incidence, with more pronounced effects for estrogen receptor α (ERα)-positive breast cancers. However, a recent systematic review with the highest level of evidence demonstrated no such relationship in post-menopausal women.

Δ-Tetrahydrocannabinol upregulates fatty acid 2-hydroxylase (FA2H) via PPARα induction: A possible evidence for the cancellation of PPARβ/δ-mediated inhibition of PPARα in MDA-MB-231 cells.

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear transcription factors, with three characterized subtypes: PPARα, PPARβ/δ, and PPARγ. The biological correlation between the two PPAR subtypes PPARα and γ and carcinogenesis is well-characterized; however, substantially less is known about the biological functions of PPARβ/δ. PPARβ/δ has been reported to repress transcription when PPARβ/δ and PPARα or PPARγ are simultaneously expressed in some cells, and MDA-MB-231 cells express functional levels of PPARβ/δ.

Repeated Exposure to 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), an Active Metabolite of Bisphenol A, Aggressively Stimulates Breast Cancer Cell Growth in an Estrogen Receptor (ER)-Dependent Manner.

Bisphenol A (BPA), recognized as an endocrine disruptor, is thought to exert its activity through a mechanism involving the activation of estrogen receptors (ERs) / However, a major problem is that very high concentrations of BPA are required (i.e., those in excess of environmental levels) for effective activation of ER/-mediated transcriptional activities in vitro, despite the BPA-induced estrogenic effects observed in vivo.

Bisphenol AF as an activator of human estrogen receptor β1 (ERβ1) in breast cancer cell lines.

Bisphenol AF (BPAF) is now recognized as one of the replacements for bisphenol A (BPA). Although considerable experimental evidence suggests that BPA is an endocrine-disrupting chemical, the toxicological profile of BPAF has been investigated in less detail than that of BPA, even at the in vitro level. BPAF has been established as an activator of estrogen receptor α (ERα) in many cell lines; however, controversy surrounds its effects on the other isoform, ERβ (i.

Bisphenol AF as an Inducer of Estrogen Receptor β (ERβ): Evidence for Anti-estrogenic Effects at Higher Concentrations in Human Breast Cancer Cells.

Bisphenols are endocrine disruptors that are widely found in the environment. Accumulating experimental evidence suggests an adverse interaction between bisphenols and estrogen signaling. Most studies have performed experiments that focused on estrogen receptor (ER) engagement by bisphenols.

Generation, repair and replication of guanine oxidation products.

Guanine is the most readily oxidized of the four DNA bases, and guanine oxidation products cause G:C-T:A and G:C-C:G transversions through DNA replication. 8-Oxo-7,8-dihydroguanine (8-oxoG) causes G:C-T:A transversions but not G:C-C:G transversions, and is more readily oxidized than guanine. This review covers four major findings.

A Novel Bongkrekic Acid Analog-Mediated Modulation of the Size of Lipid Droplets: Evidence for the Appearance of Smaller Adipocytes.

Thiazolidinediones (TZDs) are known as peroxisome proliferator-activated receptor γ (PPARγ) activators, and are used in the treatment of diabetes. Although the usefulness of TZDs has been demonstrated, some of their side effects are becoming an obstacle to their clinical applicability; edema is known to be evoked by the "structural characteristics" of TZD, but not by the PPARγ activation. Thus, novel therapeutic modalities (i.

Inhibitory modulation of human estrogen receptor α and β activities by dicyclohexyl phthalate in human breast cancer cell lines.

Phthalate esters (PAEs) are man-made compounds that are used widely in industry, and the ubiquitous exposure of humans to PAEs has been reported. Although some PAEs have been suggested to function as xenoestrogens in in vitro systems, such as human estrogen receptors (ERs) expressed in Chinese hamster ovary (CHO)-K1 cells, few studies have attempted to elucidate whether PAEs affect human ERα/ERβ-mediated signaling in human breast cancer cells (i.e.

Cadmium-induced malignant transformation of rat liver cells: Potential key role and regulatory mechanism of altered apolipoprotein E expression in enhanced invasiveness.

Cadmium is a transition metal that is classified as human carcinogen by the International Agency for Research on Cancer (IARC) with multiple target sites. Many studies using various model systems provide evidence of cadmium-induced malignancy formation in vivo or malignant cell transformation in vitro. Nonetheless, further studies are needed to completely understand the mechanisms of cadmium carcinogenicity.

Bongkrekic Acid as a Warburg Effect Modulator in Long-term Estradiol-deprived MCF-7 Breast Cancer Cells.

Background/aim: An in vitro cell model of long-term estrogen-deprived MCF-7 (LTED) cells has been utilized to analyze the re-growth mechanisms of breast cancers treated with blockers for estrogen receptor α (ERα) signaling. Bongkrekic acid (BKA) is a natural toxin isolated from coconut tempeh contaminated with the bacterium Burkholderia cocovenans.

Materials And Methods: LTED cells, MCF-7 cells and MDA-MB-231 cells were employed in the study.

Cannabidiolic acid-mediated selective down-regulation of c-fos in highly aggressive breast cancer MDA-MB-231 cells: possible involvement of its down-regulation in the abrogation of aggressiveness.

The physiological activities of cannabidiolic acid (CBDA), a component of fiber-type cannabis plants, have been demonstrated and include its function as a protector against external invasion by inducing cannabinoid-mediated necrosis (Shoyama et al., Plant Signal Behav 3:1111-1112, 2008). The biological activities of CBDA have been attracting increasing attention.

Δ(9)-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells.

We recently reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail.

Δ9-Tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.

Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects).