Ca2+-induced changes in energy metabolism and viability of melanoma cells

Abstract

Summary Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. We show here that a rise in intracellular-free calcium ion (Ca 2+ ), induced by Ca 2+ -ionophore A23187, exerted a deleterious effect on glycolysis and viability of B16 melanoma cells. Ca 2+ -ionophore caused a dose-dependent detachment of phosphofructokinase (EC 2.7.1.11), one of the key enzymes of glycolysis, from cytoskeleton. It also induced a decrease in the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two stimulatory signal molecules of glycolysis. All these changes occurred at lower concentrations of the drug than those required to induce a reduction in viability of melanoma cells. We also found that low concentrations of Ca 2+ -ionophore induced an increase in adenosine 5′-triphosphate (ATP), which most probably resulted from the increase in mitochondrial-bound hexokinase, which reflects a defence mechanism. This mechanism can no longer operate at high concentrations of the Ca 2+ -ionophore, which causes a decrease in mitochondrial and cytosolic hexokinase, leading to a drastic fall in ATP and melanoma cell death. The present results suggest that drugs which are capable of inducing accumulation of intracellular-free Ca 2+ in melanoma cells would cause a reduction in energy-producing systems, leading to melanoma cell death.

Hydrogen sulfide (H 2 S) metabolism in mitochondria and its regulatory role in energy production

“…The present study elucidates one of the molecular mechanisms for H 2 S-induced preservation of mitochondrial function. A previous study found that A23187 stimulates mitochondrial ATP production via increased activity of mitochondria-bound hexokinase (37). As shown here, A23187 also stimulates ATP production in part through mitochondrial translocation of CSE in vascular SMCs.…”

Functional expression of voltage‐gated calcium channels in human melanoma

“…An up‐regulation of L‐type channel Ca v 1.2 mRNA has been reported in colorectal cancer (Wang et al., 2000), whereas the enhanced expression of Ca v 3.1 and/or Ca v 3.2 T‐type channels are common findings in a variety of tumour cells (see Taylor et al., 2008a for review). In melanoma cells, the expression of VGCCs has not been investigated thoroughly, even when available evidence indicates that Ca 2+ signalling plays an important role in their viability and motility (Cox et al., 2002; Deli et al., 2007; Glass‐Marmor et al., 1992). In the present study we examined whether VGCCs are functionally expressed in melanoma and play a critical role in the homeostasis of these cells.…”

Functional genomics of calcium channels in human melanoma cells

“…16 On the other hand, intracellular Ca 21 oscillations are critical for the survival and migration of melanoma cells. 17,18 The melanocytic linage is characterized by a special resistance to apoptosis, which might be even attenuated during malignant transformation. It is now well established that apoptosis regulatory proteins B-cell lymphoma/leukemia-2 gene/Bax are regulators of the endoplasmic reticulum (ER) Ca 21 stores, and Ca 21 is a key mediator of apoptosis.…”