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The effect of the insecticide methoxychlor on the physiology of oral cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca concentrations ([Ca]) in human oral cancer cells (OC2) by using the Ca-sensitive fluorescent dye fura-2. Methoxychlor at 5-20 μM increased [Ca] in a concentration-dependent manner. The signal was reduced by 70% by removing extracellular Ca. Methoxychlor-induced Ca entry was not affected by nifedipine, econazole, SK&F96365 and protein kinase C modulators but was inhibited by the phospholipase A2 inhibitor aristolochic acid. In Ca-free medium, treatment with the endoplasmic reticulum Ca pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished methoxychlor-induced [Ca] rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca] rise. Inhibition of phospholipase C with U73122 did not alter methoxychlor-induced [Ca] rise. At 5-20 μM, methoxychlor killed cells in a concentration-dependent manner. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that methoxychlor (10 and 20 μM) evoked apoptosis in a concentration-dependent manner. Together, in human OC2, methoxychlor induced a [Ca] rise probably by inducing phospholipase C-independent Ca release from the endoplasmic reticulum and Ca entry via phospholipase A-sensitive channels. Methoxychlor induced cell death that may involve apoptosis. [ABSTRACT FROM AUTHOR]

1. Short-wave diathermy (SWD) is a form of radiofrequency radiation that is used therapeutically by physiotherapists. The cellular mechanisms of SWD are unclear. The present study was performed to explore the effect of different conditions of short-wave exposure on the proliferation of cultured human chondrocytes. 2. Cells exposed to short waves once per day for seven consecutive days exhibited a significant increase in proliferation by 42% compared with the control cells. In cells that were treated with short waves twice per day for seven consecutive days, or only once on Day 1 and then examined for proliferation on Day 7, cell proliferation was greater than the control cells by 40% and 30%, respectively. 3. Given the importance of mitogen-activated protein kinases (MAPK) in the proliferation of different cell types, efforts were extended to explore the role of three major types of MAPK; that is, extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal protein kinase (JNK) and p38. 4. It was found that the level of phosphorylated ERK (phospho-ERK 1 and ERK 2) increased significantly within 5–120 min following consecutive exposure to short waves for 7 days. Exposure to short waves failed to alter the intensity of phosphorylated JNK and p38 within 0–240 min. 5. Cells were exposed to short waves once for seven consecutive days in the presence of 0, 10 µmol/L, 20 µmol/L or 50 µmol/L PD98059 (an ERK inhibitor). PD98059 totally inhibited short waves-induced enhancement of proliferation without altering normal control viability. In the presence of short waves and PD98059, the cell viability was lower than the normal control. Together, the data suggest that short waves could increase proliferation in human chondrocytes through activation of the ERK pathway, which is also involved in maintaining normal cell proliferation under physiological conditions. [ABSTRACT FROM AUTHOR]

In human MG63 osteosarcoma cells, the effect of flurbiprofen on intracellular Ca2+ concentrations ([Ca2+]i) and proliferation was explored. The proliferation was enhanced by 20–120 μM flurbiprofen, and was decreased by 140–200 μM flurbiprofen. The effect of flurbiprofen on the increases in cytosolic free Ca2+ levels ([Ca2+]i) induced by ATP, bradykinin, histamine and thapsigargin (an inhibitor of the endoplasmic reticulum Ca2+ ATPase), was examined. In cell preincubated with 20 or 80 μM flurbiprofen, the [Ca2+]i increases induced by all agonists were attenuated. In the presence of 20 μM flurbiprofen, the decreased [Ca2+]i responses with the agonists were attributed to a defective Ca2+ influx because this decrease was unobserved in agonists-induced [Ca2+]i increases in the absence of extracellular Ca2+. In the presence of 80 μM flurbiprofen, both the Ca2+ influx component and the Ca2+ releasing (from organelles) component were defective. These results suggest that flurbiprofen could alter proliferation and inhibit [Ca2+]i increases. [ABSTRACT FROM AUTHOR]

The effect of the antidepressant nortriptyline, on bone cells is unknown. In human osteosarcoma MG63 cells, the effect of nortriptyline on intracellular Ca2+ concentration ([Ca2+]i) and proliferation was measured by using fura-2 and tetrazolium, respectively. Nortriptyline (≥10μM) caused a[Ca2+]i rise in a concentration-dependent manner (EC50=200μM). Nortriptyline-induced[Ca2+]i rise was prevented by 60% by removal of extracellular Ca2+ but was not altered by voltage-gated Ca2+ channel blockers. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic[Ca2+]i rise, after which the increasing effect of nortriptyline on[Ca2+]i was abolished; also, pretreatment with nortriptyline abolished thapsigargin-induced[Ca2+]i increase. U73122, an inhibitor of phospholipase C, did not affect nortriptyline-induced[Ca2+]i rise; however, activation of protein kinase C decrease nortriptyline-induced[Ca2+]i rise by 32%. Overnight incubation with 50 and 100μM nortriptyline killed 78% and 97% of cells, respectively; while 10μM nortriptyline had no effect. These data suggest that nortriptyline rapidly increases[Ca2+]i in human osteosarcoma cells by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release, and is cytotoxic at high concentrations. [ABSTRACT FROM AUTHOR]