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Background Objectives Methods Results Conclusion Oxatomide, an antihistamine drug of the diphenylmethylpiperazine family, has anti‐inflammatory effects in airway disease. Because oxatomide was shown to cause diverse physiological responses in several cell models, the impact of oxatomide on Ca2+ signaling and its related physiological effects has not been explored in IMR‐90 human fetal lung fibroblasts.This study assessed the effect of oxatomide on cell viability and intracellular free Ca2+ concentrations ([Ca2+]i) and examined whether oxatomide‐induced cytotoxicity through Ca2+ signaling in IMR‐90 cells.Cell viability was measured by the cell proliferation reagent (WST‐1). [Ca2+]i was measured by the Ca2+‐sensitive fluorescent dye fura‐2.Oxatomide (10–40 μM) concentration dependently reduced cell viability and induced [Ca2+]i rises in IMR‐90 cells. This cytotoxic effect was reversed by chelation of cytosolic Ca2+ with BAPTA‐AM. In terms of Ca2+ signaling, oxatomide‐caused Ca2+ entry was inhibited by modulators of store‐operated Ca2+ channels (2‐APB and SKF96365) and protein kinase C (PKC) inhibitor (GF109203X). Furthermore, oxatomide‐induced Ca2+ influx was confirmed by Mn2+‐induced quench of fura‐2 fluorescence. In a Ca2+‐free medium, preincubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited oxatomide‐evoked [Ca2+]i rises. Conversely, treatment with oxatomide abolished thapsigargin‐induced [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 also inhibited oxatomide‐caused [Ca2+]i rises.In IMR‐90 cells, oxatomide‐induced cytotoxicity by preceding [Ca2+]i rises involving PKC‐sensitive store‐operated Ca2+ entry and PLC‐dependent Ca2+ release from the endoplasmic reticulum. BAPTA‐AM, with its Ca2+ chelating effects, may be a potential compound for preventing oxatomide‐induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a type of mycotoxin commonly found in raw and processed foods. It is essential to be aware of this toxin, as it can harm your health if consumed in high quantities. OTA can induce toxic effects in various cell models. However, a more comprehensive understanding of the harmful effects of OTA on human astrocytes is required. This study evaluated OTA's neurotoxic effects on the Gibco® Human Astrocyte (GHA) cell line, its underlying mechanisms, and the antioxidant N‐acetylcysteine (NAC) ability to prevent them. OTA exposure within 5–30 μM has induced concentration‐dependent cytotoxicity. In the OTA‐treated cells, the levels of reactive oxygen species (ROS) were found to be significantly increased, while the glutathione (GSH) contents were found to decrease considerably. The western blotting of OTA‐treated cells has revealed increased Bax, cleaved caspase‐9/caspase‐3 protein levels, and increased Bax/Bcl‐2 ratio. In addition, exposure to OTA has resulted in the induction of antioxidant responses associated with the protein expressions of Nrf2, HO‐1, and NQO1. On the other hand, the pretreatment with NAC has partially alleviated the significant toxic effects of OTA. In conclusion, our findings suggest that oxidative stress and apoptosis are involved in the OTA‐induced cytotoxicity in GHA cells. NAC could act as a protective agent against OTA‐induced oxidative damage. Our findings suggest that oxidative stress and apoptosis are involved in the ochratoxin A (OTA)‐induced cytotoxicity in Gibco® Human Astrocyte (GHA) cells. N‐acetylcysteine (NAC) could act as a protective agent against OTA‐induced oxidative damage. This study has reported that NAC could alleviate the OTA‐induced cytotoxicity in GHA cells for the first time. It has also elucidated some of its mechanisms, providing a new perspective for treating OTA‐induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Organophosphate pesticides (OPs), which are among the most widely used synthetic chemicals for the control of a wide variety of pests, are however associated with various adverse reactions in animals and humans. Chlorpyrifos, an OP, has been shown to cause various health complications due to ingestion, inhalation, or skin absorption. The mechanisms underlying the adverse effect of chlorpyrifos on neurotoxicity have not been elucidated. Therefore, we aimed to determine the mechanism of chlorpyrifos‐induced cytotoxicity and to examine whether the antioxidant vitamin E (VE) ameliorated these cytotoxic effects using DBTRG‐05MG, a human glioblastoma cell line. The DBTRG‐05MG cells were treated with chlorpyrifos, VE, or chlorpyrifos plus VE and compared with the untreated control cells. Chlorpyrifos induced a significant decrease in cell viability and caused morphological changes in treated cultures. Furthermore, chlorpyrifos led to the increased production of reactive oxygen species (ROS) accompanied by a decrease in the level of reduced glutathione. Additionally, chlorpyrifos induced apoptosis by upregulating the protein levels of Bax and cleaved caspase‐9/caspase‐3 and by downregulating the protein levels of Bcl‐2. Moreover, chlorpyrifos modulated the antioxidant response by increasing the protein levels of Nrf2, HO‐1, and NQO1. However, VE reversed the cytotoxicity and oxidative stress induced by chlorpyrifos treatment in DBTRG‐05MG cells. Overall, these findings suggest that chlorpyrifos causes cytotoxicity through oxidative stress, a process that may play an important role in the development of chlorpyrifos‐associated glioblastoma. [ABSTRACT FROM AUTHOR]

Chlorpromazine, an antipsychotic medication, is conventionally applied to cope with the psychotic disorder such as schizophrenia. In cellular studies, chlorpromazine exerts many different actions through calcium ion (Ca2+) signaling, but the underlying pathways are elusive. This study explored the effect of chlorpromazine on viability, Ca2+ signaling pathway and their relationship in glial cell models (GBM 8401 human glioblastoma cell line and Gibco® Human Astrocyte (GHA)). First, chlorpromazine between 10 and 40 μM induced cytotoxicity in GBM 8401 cells but not in GHA cells. Second, in terms of Ca2+ homeostasis, chlorpromazine (10–30 μM) increased intracellular Ca2+ concentrations ([Ca2+]i) rises in GBM 8401 cells but not in GHA cells. Ca2+ removal reduced the signal by approximately 55%. Furthermore, chelation of cytosolic Ca2+ with BAPTA-AM reduced chlorpromazine (10–40 μM)-induced cytotoxicity in GBM 8401 cells. Third, in Ca2+-containing medium of GBM 8401 cells, chlorpromazine-induced Ca2+ entry was inhibited by the modulators of store-operated Ca2+ channel (2-APB and SKF96365). Lastly, in Ca2+-free medium of GBM 8401 cells, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin completely inhibited chlorpromazine-increased [Ca2+]i rises. Conversely, treatment with chlorpromazine abolished thapsigargin-increased [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished chlorpromazine-increased [Ca2+]i rises. Together, in GBM 8401 cells but not in GHA cells, chlorpromazine increased [Ca2+]i rises by Ca2+ influx via store-operated Ca2+ entry and PLC-dependent Ca2+ release from the endoplasmic reticulum. Moreover, the Ca2+ chelator BAPTA-AM inhibited cytotoxicity in chlorpromazine-treated GBM 8401 cells. Therefore, Ca2+ signaling was involved in chlorpromazine-induced cytotoxicity in GBM 8401 cells. [ABSTRACT FROM AUTHOR]

Haloperidol, a typical antipsychotic medication, has been shown to possess various biological effects in different brain models. However, the impact of haloperidol on Ca2+ signaling in astrocytes is elusive. This study explored the effect of haloperidol on cytosolic free Ca2+ levels ([Ca2+]i) and viability, and established these two connections in Gibco® Human Astrocytes (GHAs) and DI TNC1 rat astrocytes. Haloperidol (5–20 μM) caused [Ca2+]i rises in a concentration-dependent manner in GHAs but not in DI TNC1 cells. Furthermore, removal of extracellular Ca2+ reduced haloperidol's effect by approximately 30% in GHAs. Haloperidol (20–40 μM) evoked concentration-dependent cytotoxicity in GHAs and DI TNC1 cells. However, chelating cytosolic Ca2+ with the Ca2+ chelator BAPTA/AM significantly reversed haloperidol's cytotoxicity only in GHAs. In GHAs, haloperidol-induced Ca2+ entry was inhibited by store-operated Ca2+ modulators (2-APB and SKF96365) and the protein kinase C (PKC) inhibitor GF109203X. This Ca2+ entry induced by haloperidol was confirmed by Mn2+ entry-induced quench of fura-2 fluorescence. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished haloperidol-induced [Ca2+]i rises. Conversely, treatment with haloperidol inhibited 45% of BHQ-evoked [Ca2+]i rises. Moreover, haloperidol-induced Ca2+ release from the endoplasmic reticulum was abolished by inhibition of phospholipase C (PLC) by U73122. Together, in GHAs but not in DI TNC1 cells, haloperidol caused Ca2+-associated cell death, induced Ca2+ entry via PKC-sensitive store-operated Ca2+ channels, and evoked PLC-dependent Ca2+ release from the endoplasmic reticulum. The protective effect of Ca2+ chelating on haloperidol-induced cytotoxicity in human astrocytes was also demonstrated. [ABSTRACT FROM AUTHOR]

Literature has shown that diosgenin, a naturally occurring sapogenin, inducedcytotoxic effects in many cancer models. This study investigated the effect of diosgenin on intracellular Ca2+ concentration ([Ca2+]i) and cytotoxicity in PC3 human prostate cancer cells. Diosgenin (250‐1000 μM) caused [Ca2+]i rises which was reduced by Ca2+ removal. Treatment with thapsigargin eliminated diosgenin‐induced [Ca2+]i increases. In contrast, incubation with diosgeninabolished thapsigargin‐caused [Ca2+]i increases. Suppression of phospholipase C with U73122 eliminated diosgenin‐caused [Ca2+]i increases. Diosgenin evoked Mn2+ influx suggesting that diosgenin induced Ca2+ entry. Diosgenin‐induced Ca2+influx was suppressed by PMA, GF109203X, and nifedipine, econazole, or SKF96365. Diosgenin (250‐600 μM) concentration‐dependently decreased cell viability. However, diosgenin‐induced cytotoxicity was not reversed by chelation of cytosolic Ca2+ with BAPTA/AM. Together, diosgenin evoked [Ca2+]i increases via Ca2+ release and Ca2+ influx, and caused Ca2+‐non‐associated deathin PC3 cells. These findings reveal a newtherapeutic potential of diosgenin for human prostate cancer. [ABSTRACT FROM AUTHOR]

Summary: Glyburide is an agent commonly used to treat type 2 diabetes and also affects various physiological responses in different models. However, the effect of glyburide on Ca2+ movement and its related cytotoxicity in prostate cancer cells is unclear. This study examined whether glyburide altered Ca2+ signalling and viability in PC3 human prostate cancer cells and investigated those underlying mechanisms. Intracellular Ca2+ concentrations ([Ca2+]i) in suspended cells were measured by using the fluorescent Ca2+‐sensitive dye fura‐2. Cell viability was examined by WST‐1 assay. Glyburide at concentrations of 100–1000 μM induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 60%. In Ca2+‐containing medium, glyburide‐induced Ca2+ entry was inhibited by 60% by protein kinase C (PKC) activator (phorbol 12‐myristate 13 acetate, PMA) and inhibitor (GF109203X), and modulators of store‐operated Ca2+ channels (nifedipine, econazole and SKF96365). Furthermore, glyburide induced Mn2+ influx suggesting of Ca2+ entry. In Ca2+‐free medium, inhibition of phospholipase C (PLC) with U73122 significantly inhibited glyburide‐induced [Ca2+]i rises. Treatment with the endoplasmic reticulum (ER) Ca2+ pump inhibitor 2,5‐di‐tert‐butylhydroquinone (BHQ) abolished glyburide‐evoked [Ca2+]i rises. Conversely, treatment with glyburide abolished BHQ‐evoked [Ca2+]i rises. Glyburide at 100–500 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid‐acetoxymethyl ester (BAPTA/AM). Together, in PC3 cells, glyburide induced [Ca2+]i rises by Ca2+ entry via PKC‐sensitive store‐operated Ca2+ channels and Ca2+ release from the ER in a PLC‐dependent manner. Glyburide also caused Ca2+‐independent cell death. This study suggests that glyburide could serve as a potential agent for treatment of prostate cancer. [ABSTRACT FROM AUTHOR]