Abstract
Currently, there is no appropriate treatment option for patients with sorafenib-resistant hepatocellular carcinoma (HCC). Meanwhile, pronounced anticancer activities of newly-developed mitochondria-accumulating self-assembly peptides (Mito-FF) have been demonstrated. This study intended to determine the anticancer effects of Mito-FF against sorafenib-resistant Huh7 (Huh7-R) cells. Compared to sorafenib, Mito-FF led to the generation of relatively higher amounts of mitochondrial reactive oxygen species (ROS) as well as the greater reduction in the expression of antioxidant enzymes (P < 0.05). Mito-FF was found to significantly promote cell apoptosis while inhibiting cell proliferation of Huh7-R cells. Mito-FF also reduces the expression of antioxidant enzymes while significantly increasing mitochondrial ROS in Huh7-R cells. The pro-apoptotic effect of Mito-FFs for Huh7-R cells is possibly caused by their up-regulation of mitochondrial ROS, which is caused by the destruction of the mitochondria of HCC cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Apoptosis / drug effects
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Delivery Systems / methods*
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / physiology
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Humans
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Liver Neoplasms / drug therapy
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Mitochondria / metabolism
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Organophosphorus Compounds / pharmacology
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Organophosphorus Compounds / therapeutic use*
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Peptides / metabolism
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Peptides / pharmacology*
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Peptides / therapeutic use
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Phenylalanine / pharmacology
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Phenylalanine / therapeutic use*
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Pyrenes / pharmacology
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Pyrenes / therapeutic use*
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Reactive Oxygen Species / metabolism
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Sorafenib / pharmacology
Substances
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Antineoplastic Agents
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Organophosphorus Compounds
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Peptides
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Pyrenes
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Reactive Oxygen Species
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mito-FF
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tributylmethyl phosphonium chloride
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Phenylalanine
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pyrene
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Sorafenib