Thermal sensitisation by lonidamine of human melanoma cells grown at low extracellular pH.

Purpose: This study tested the ability of lonidamine (LND), a clinically applicable inhibitor of monocarboxylate transporters (MCT), to thermally sensitise human melanoma cells cultured at a tumour-like extracellular pH (pHe) 6.7.

Materials And Methods: Human melanoma DB-1 cells cultured at pHe 6.

Inhibiting induction of heat shock proteins as a strategy to enhance cancer therapy.

Cancer treatments that incorporate thermal therapy and some systemic therapies induce the production of heat shock or stress proteins. The induced heat shock proteins could lessen the effect of the therapy by inhibiting apoptotic signaling and by acting as molecular chaperones to prevent irreversible cellular damage. Strategies that prevent the induction of heat shock proteins would result in more apoptosis and necrosis, improving the cancer therapy.

Intracellular acidification abrogates the heat shock response and compromises survival of human melanoma cells.

This study tests the hypothesis that lowering intracellular pH (pHi) in melanoma cells grown at low extracellular pH (pHe) selectively abrogates 42 degrees C-induced heat shock protein (HSP) expression and reduces survival. Cells were acidified by a combination of a 0.2-pH-unit decrease in pHe coupled with the lactate/H+ transport inhibitor alpha-cyano-4-hydroxy-cinnamic acid (CNCn).

Cellular Senescence: Ex Vivo p53-Dependent Asymmetric Cell Kinetics.

Although senescence is a defining property of euploid mammalian cells, its physiologic basis remains obscure. Previously, cell kinetics properties of normal tissue cells have not been considered in models for senescence. We now provide evidence that senescence is in fact the natural consequence of normal in vivo somatic stem cell kinetics extended in culture.