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      Synergism between apple procyanidins and lysosomotropic drugs: potential in chemoprevention.

      Anticancer research
      metabolism, Antimalarials, pharmacology, Antioxidants, Apoptosis, drug effects, Biflavonoids, Catechin, Cell Proliferation, Chemoprevention, Chloroquine, Colonic Neoplasms, pathology, prevention & control, Drug Synergism, Humans, Lysosomes, Malus, chemistry, Oxidoreductases Acting on CH-NH Group Donors, antagonists & inhibitors, Phenylalanine, analogs & derivatives, Proanthocyanidins, Putrescine, Tumor Cells, Cultured

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          Abstract

          Procyanidins are apple constituents with potential in colon cancer chemoprevention. Human colon cancer derived metastatic cells (SW620), growing under standardized conditions, were exposed to procyanidins and lysosomotropic compounds. Growth, apoptosis and lysosomal integrity was determined using published methods. Lysosomotropic drugs (MDL 72527, phenylalanine methylester and chloroquine) amplified procyanidin-induced growth inhibition and apoptosis in SW620 cells at non-cytotoxic concentrations. The improved toxicity of the drug combinations relies primarily on the enhancement of lysosomal membrane permeability. Combinations with non-toxic concentrations of lysosomotropic compounds improve the anti-carcinogenic properties of apple procyanidins.

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