Effects of Ascorbic Acid on Calcium Signaling in Tumor Cells

Abstract

Effects of ascorbic acid on calcium homeostasis of human laryngeal carcinoma cells were studied. Intracellular concentration of free calcium and intracellular pH were measured by fluorescent analysis. Ascorbic acid in concentrations of 3-10 mM caused pH drop and sharply increased concentrations of free Ca ions in HEp-2 cells. Intracellular concentration of free Ca ions resulted from Ca ion release from the thapsigargin-sensitive Ca depots.

Redox Regulation of Calcium Signaling in Cancer Cells by Ascorbic Acid Involving the Mitochondrial Electron Transport Chain

“…In a previous study, ascorbic acid was found to cause a transient increase in [Ca 2+ ] cyt in human larynx carcinoma HEp-2 cells accompanied by depletion of intracellular thapsigargin-sensitive calcium stores [16]. Thapsigargin is known to induce Ca 2+ release, from mitochondria and inositol-1,4,5-triphosphate-responsive Ca 2+ stores.…”

“…The RET is observed under conditions of high Δ ψ [19]. Previously we have shown that ascorbate at high concentrations induces the decrease in intracellular pH value that can lead to the increase in Δ ψ [16]. In such conditions, rotenone inhibits ROS production in mitochondria.…”

“…Earlier was supposed that selectivity of ascorbate effect on cancer cells was mediated by an altered acid-base balance in tumor tissues [16]. Changes in the activity of electron transport chain components observed in many cancer cells including carcinoma cells [31] may also promote cytotoxic action of ascorbate towards cancer cells.…”

“…It was also shown that even in the presence of transition metal ions and H 2 O 2 , ascorbate acted as an antioxidant that prevented lipid peroxidation in human plasma in vitro [15]. Previously, we have found that ascorbic acid regulates calcium signaling in human larynx carcinoma cells [16]. Ascorbate at concentrations in the range 3–10 mM activated cytosol pH value decrease and Ca 2+ release from thapsigargin-sensitive intracellular Ca 2+ stores.…”

Ascorbic Acid Induces Necrosis in Human Laryngeal Squamous Cell Carcinoma via ROS, PKC, and Calcium Signaling

“…Intracellular calcium is an important signaling molecule for numerous cell responses, including necrosis (Syntichaki and Tavernarakis, ; Li et al, ). It is known that ascorbic acid treatment induces a sharp increment in the cytosolic calcium concentration in tumor cells (Martinovich et al, ). The present study showed that cytosolic calcium levels were increased in Hep2 cells after ascorbic acid treatment and that pretreatment with the calcium chelator BAPTA‐AM dramatically inhibited ascorbic acid‐induced necrotic cell death in these Hep2 cells.…”