Anticancer Effects of Thymoquinone through the Antioxidant Activity, Upregulation of Nrf2, and Downregulation of PD-L1 in Triple-Negative Breast Cancer Cells.

The variety of therapies available for treating and preventing triple-negative breast cancer (TNBC) is constrained by the absence of progesterone receptors, estrogen receptors, and human epidermal growth factor receptor 2. Nrf2 (nuclear factor-erythroid 2-related factor), and PD-L1 (program cell death ligand 1), a downstream signaling target, have a strong correlation to oxidative stress and inflammation, major factors in the development and progression of TNBC. In this study, the genetically distinct MDA-MB-231 and MDA-MB-468 TNBC cells were treated with the natural component thymoquinone (TQ).

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells.

Breast cancer (BC) is the most common cancer in women worldwide, and it is one of the leading causes of cancer death in women. triple-negative breast Cancer (TNBC), a subtype of BC, is typically associated with the highest pathogenic grade and incidence in premenopausal and young African American (AA) women. Chemotherapy, the most common treatment for TNBC today, can lead to acquired resistance and ineffective treatment.

Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment.

To date, the tumor microenvironment (TME) has gained considerable attention in various areas of cancer research due to its role in driving a loss of immune surveillance and enabling rapid advanced tumor development and progression. The TME plays an integral role in driving advanced aggressive breast cancers, including triple-negative breast cancer (TNBC), a pivotal mediator for tumor cells to communicate with the surrounding cells via lymphatic and circulatory systems. Furthermore, the TME plays a significant role in all steps and stages of carcinogenesis by promoting and stimulating uncontrolled cell proliferation and protecting tumor cells from the immune system.

Triple Isozyme Lactic Acid Dehydrogenase Inhibition in Fully Viable MDA-MB-231 Cells Induces Cytostatic Effects That Are Not Reversed by Exogenous Lactic Acid.

A number of aggressive human malignant tumors are characterized by an intensified glycolytic rate, over-expression of lactic acid dehydrogenase A (LDHA), and subsequent lactate accumulation, all of which contribute toward an acidic peri-cellular immunosuppressive tumor microenvironment (TME). While recent focus has been directed at how to inhibit LDHA, it is now becoming clear that multiple isozymes of LDH must be simultaneously inhibited in order to fully suppress lactic acid and halt glycolysis. In this work we explore the biochemical and genomic consequences of an applied triple LDH isozyme inhibitor (A, B, and C) (GNE-140) in MDA-MB-231 triple-negative breast cancer cells (TNBC) cells.

Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks.

Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis.

Cocaine potentiates an inflammatory response in C6 astroglia-like cells.

Cocaine is a highly addictive drug that mediates its effect through altering dopamine metabolism in the central nervous system (CNS), resulting in a feeling of euphoria. Owing to its high lipophilicity, cocaine easily crosses the blood brain barrier of the CNS and reaches various domains of the brain, where it can trigger cellular damage. Cocaine-induced CNS damage may arise due to increased levels of free radicals and nitric oxide (NO) in immunecompetent astroglial cells.

Identification of cytotoxic markers in methamphetamine treated rat C6 astroglia-like cells.

Methamphetamine (METH) is a powerfully addictive psychostimulant that has a pronounced effect on the central nervous system (CNS). The present study aimed to assess METH toxicity in differentiated C6 astroglia-like cells through biochemical and toxicity markers with acute (1 h) and chronic (48 h) treatments. In the absence of external stimulants, cellular differentiation of neuronal morphology was achieved through reduced serum (2.

Cellular and molecular responses to acute cocaine treatment in neuronal-like N2a cells: potential mechanism for its resistance in cell death.

Cocaine is a highly abused drug that causes psychiatric and neurological problems. Its entry into neurons could alter cell-biochemistry and contribute in the manifestation of early pathological symptoms. We have previously shown the acute cocaine effects in rat C6 astroglia-like cells and found that these cells were highly sensitive to cocaine in terms of manifesting certain pathologies known to underlie psychological disorders.

Identification of biochemical and cytotoxic markers in cocaine treated PC12 cells.

Cocaine is one of the powerful addictive drugs, widely abused in most Western countries. Because of high lipophilic nature, cocaine easily reaches various domains of the central nervous system (CNS) and triggers different levels of cellular toxicity. The aim of this investigation was to reproduce cocaine toxicity in differentiated PC12 cells through quantitative knowledge on biochemical and cytotoxicity markers.

Modulation of cytokines and chemokines expression by NAC in cadmium chloride treated human lung cells.

Cadmium (Cd), is one of the most hazardous metals found in the environment. Cd exposure through inhalation has been linked to various diseases in lungs. It was shown that Cd induces proinflammatory cytokines through oxidative stress mechanism.

Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells.

Cadmium is an environmentally hazardous metal, which causes toxicity in humans. Inhalation of cigarette smoke and industrial fumes containing cadmium are sources of cadmium exposure. It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys.

N-acetyl cysteine mitigates the acute effects of cocaine-induced toxicity in astroglia-like cells.

Cocaine has a short half-life of only about an hour but its effects, predominantly on the central nervous system (CNS), are fairly long-lasting. Of all cells within the CNS, astrocytes may be the first to display cocaine toxicity owing to their relative abundance in the brain. Cocaine entry could trigger several early response changes that adversely affect their survival, and inhibiting these changes could conversely increase their rate of survival.

Selective anticancer activity of neurotoxin 1-methyl-4-phenylpyridinium on non-small cell lung adenocarcinoma A549 cells.

Background: Lung cancer is the second leading cause of mortality among men and women in the U.S. Among different varieties of lung cancer, the non-small cell lung cancer (NSCLC) has the highest frequency comprising about 85% of cases.

Milk thistle seed extract protects rat C6 astroglial cells from acute cocaine toxicity.

Cocaine is a powerful addictive drug, widely abused in most Western countries. It easily reaches various domains within and outside of the central nervous system (CNS), and triggers varying levels of cellular toxicity. No pharmacological treatment is available to alleviate cocaine-induced toxicity in the cells without side-effects.

Chemoprotective effect of monoisoamyl 2, 3-dimercaptosuccinate (MiADMS) on cytokines expression in cadmium chloride treated human lung cells.

Cadmium is commercially profitable element, but it causes toxicity in humans and animals leading to diseases in various organs. The main route of cadmium exposure to humans is through inhalation. Lungs respond to insult through secretion of cytokines.

Attenuating effect of N-acetyl-L-cysteine against acute cocaine toxicity in rat C6 astroglial cells.

Astroglial cells are one of the most abundant cell types in the mammalian brain functioning in neuronal survival and in maintenance of fundamental patterns of circuitry. To date, no study has been conducted regarding the short-term impact of cocaine on these cells in cultures. The present study aimed to investigate acute cocaine (1 h) treatment on cell viability in rat C6 astroglial cells.

Regulation of mammalian MOR-1 gene expression after chronic treatment with morphine.

Morphine is an effective analgesic that acts by binding to the µ-opioid receptor (MOR) coded in the human by the OPRM1 gene. In the present study, we investigated the regulation of µ-opioid receptor (MOR-1) mRNA levels in all-trans-retinoic acid-differentiated SH-SY5Y human neuroblastoma cells under in vitro conditions with 10 µM morphine treatment for 24 h. In addition, we measured the MOR-1 levels in recombinant Chinese hamster ovary (CHO) cells, transfected with human µ-opioid receptor gene (hMOR) with 10 µM morphine treatment for 24 h.

Effects of chronic cocaine in rat C6 astroglial cells.

Investigations with astroglial cells carry equal importance as those with neurons in drug abuse studies. The present study was aimed to investigate the effect of chronic cocaine administration on cell viability, nitric oxide (NO) production, general respiratory status of mitochondria and total protein levels in rat astroglioma cells after 24 h of treatment. In addition, the effect of cocaine was assessed for 24 h on brine shrimp larvae in order to study their sensitivity to the drug.

Autoxidation of gallic acid induces ROS-dependent death in human prostate cancer LNCaP cells.

Background: Prostate cancer is the second most common cause of mortality. Gallic acid (GA) is a natural polyphenol, and we tested its in-vitro cytotoxicity after 24 h in prostate cancer LNCaP cells.

Materials And Methods: GA autoxidation was measured fluorimetrically for H(2)O(2), and O(2)(•-) radicals by chemiluminescence.

Effect of ascorbic acid and hydrogen peroxide on mouse neuroblastoma cells.

Ascorbic acid is one of the antioxidant compounds widely used against free radical stress. The present study was undertaken to examine whether ascorbic acid and hydrogen peroxide (H2O2), alone or in combination, could influence cell viability. The murine neuroblastoma cell line, N2a, was used to perform a dose response curve for ascorbic acid.

Differential cytotoxicity of triphala and its phenolic constituent gallic acid on human prostate cancer LNCap and normal cells.

Background: Prostate cancer is one of the most commonly diagnosed solid malignancies among US men. We identified gallic acid (GA) as a major bioactive cytotoxic constituent of a polyherbal Ayurvedic formulation - triphala (TPL). Both TPL and GA were evaluated on (AR)(+) LNCaP prostate cancer and normal epithelial cells.

Mitigative action of monoisoamyl-2,3-dimercaptosuccinate (MiADMS) against cadmium-induced damage in cultured rat normal liver cells.

Cadmium is non-essential, carcinogenic and multitarget pollutant in the environment. Monoisoamyl-2,3-dimercaptosuccinate (MiADMS) is an ester of dimercaptosuccinic acid that acts as an antioxidant and chelator. Therefore, the mitigative action of MiADMS on viability, morphology, antioxidative enzymes and cell cycle were studied on rat liver cells treated with cadmium chloride (CdCl2).

Protective effects of N-acetylcysteine against cadmium-induced damage in cultured rat normal liver cells.

In this study, the protective effects of N-acetylcysteine (NAC), a precursor of reduced glutathione, were studied by measuring the viability, the levels of antioxidant enzymes, and by analyzing the cell cycle in cadmium (Cd)-treated rat liver cells. The cells were treated with 150 µM CdCl2 alone or co-treated with 150 µM CdCl2 and 5 mM NAC (2 h pre-, simultaneous or 2 h post-treatment) for 24 h. The viability of the cells treated with 150 µM CdCl2 alone decreased to 40.

The protective role of D-glucose against 1-methyl-4-phenylpyridinium ion (MPP+): induced mitochondrial dysfunction in C6 astroglial cells.

Impaired mitochondrial function in glial and neuronal cells in the substantia nigra is one of the most likely causes of Parkinson's disease. In this study, we investigated the protective role of glucose on early key events associated with MPP(+)-induced changes in rat C6 astroglial cells. Studies were carried out to examine alterations in mitochondrial respiratory status, membrane potential, glutathione levels, and cell cycle phase inhibition at 48 h in 2 and 10 mM glucose in media.