Effect of Methoxychlor on Ca²⁺ Handling and Viability in OC2 Human Oral Cancer Cells

Abstract

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 2+ concentrations ([Ca 2+ ] i ) in human oral cancer cells (OC2) by using the Ca 2+ -sensitive fluorescent dye fura-2. Methoxychlor at 5-20 lM increased [Ca 2+ ] i in a concentration-dependent manner. The signal was reduced by 70% by removing extracellular Ca 2+. Methoxychlor-induced Ca 2+ 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 Methoxychlor ( fig. 1) is a broad-spectrum chlorinated insecticide, which is an organochlorine derivative of dichlorodiphenyl-trichloroethane (DDT) but with a much lower toxicity. Methoxychlor has become a substitute for the banned DDT and is commonly used in the USA to control insects on agricultural crops, livestock, animal feeds and household pets [1]. Because of work, chemical application and food ingestion, human beings as well as wildlife species are easily exposed to methoxychlor [2]. Methoxychlor acts as a proestrogen, and metabolism of this chemical by liver microsomes produces mono-, bis-, tris-hydroxy and catechol-M, which are oestrogenic in nature. The most active oestrogenic form is 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) [3]. Recent findings have revealed that methoxychlor reduces fertility in male rats [4] and decreases the ability of ovarian cells to synthesize and secrete hormones in female rats [5]. Such adverse effects found in the male and female rat reproductive systems have not been shown in human beings.Methoxychlor is shown to increase cytosolic Ca ] i trigger key cellular functions such as contraction of myofilaments, secretion of hormones and neurotransmitters and modulation of metabolism [7,8]. Ca 2+ also has a major function in triggering mitotic division in some cell types (e.g. T lymphocytes and of oocytes) and conversely in the regulation of cell death [9]. Evidence shows that Ca 2+ release from the endoplasmic reticulum and capa- ] i that form Ca 2+ spikes and waves [7].Programmed cell death (apoptosis) is an essential mechanism to eliminate unwanted cells during the development and homoeostasis of multicellular organisms. This extremely well-organized process involves DNA fragmentation,

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells

“…This signal transduction enzyme was implicated in downregulation of GJIC in response to various toxicants, including DDT, PCB153, dicumylperoxide, perfluorooctanoic acid, or polycyclic aromatic hydrocarbons (Sovadinova et al, 2015). However, our study might be one of the rare reports suggesting activation of phospholipases in response to MXC (Cheng et al, 2012;Tseng et al, 2011), and possibly the first one demonstrating the key role of rapid phospholipase activation in cell responses to VIN exposure. Future studies should address the signaling events upstream and downstream of PC-PLC activation and their role in the mechanisms of GJIC inhibition and MAPK activation.…”

Effect of Methoxychlor on Ca2+ Movement and Viability in MDCK Renal Tubular Cells

“…Furthermore, it seems that methoxychlor‐induced [Ca 2+ ] i rise is phospholipase C dependent, because the response was inhibited when phospholipase C activity was inhibited by U73122. In contrast, methoxychlor was shown to increase [Ca 2+ ] i in OC2 human oral cancer cells in a phospholipase C‐independent manner . Thus, methoxychlor appears to affect [Ca 2+ ] i differently in different cell types.…”

“…The effect of methoxychlor on other cell types has been studied. Methoxychlor is shown to alter Ca 2+ handling and viability in human oral cancer cells and to increase [Ca 2+ ] i in human umbilical vein endothelial cells . In thymocytes and immunocytes, methoxychlor is shown to induce apoptosis .…”

Effect of the pesticide, deltamethrin, on Ca2+signaling and apoptosis in OC2 human oral cancer cells

“…The OC2 oral cancer cell line is a useful model for evaluating toxicity in oral mucosal epithlelial cells. It has been shown, in the OC2 cell line, that [Ca 2+ ] i can increase in response to stimulation of various agents, such as methoxychlor (Tseng et al, 2011), thimerosal (Kuo et al, 2009) and fendiline , by causing Ca 2+ entry and Ca 2+ release. Therefore, this study explored the potential oral toxicity of deltamethrin in the OC2 cell line.…”