Abstract
5-Fluorouracil (5-FU) alone or in combination with other drugs is the main basis of chemotherapeutic treatment in colorectal cancer although patients with microsatellite instability generally show resistance to 5-FU treatment. The present investigation is focussed on the mechanistic insight of a pure herbal carbazole alkaloid, mahanine, as a single or in combination with 5-FU in colon cancer. We demonstrated that mahanine-induced apoptosis involved reactive oxygen species (ROS)-mediated nuclear accumulation of PTEN and its interaction with p53/p73. Mahanine and 5-FU in combination exerted synergistic inhibitory effect on cell viability. This combination also enhanced ROS production, increased tumour suppressor proteins and suppressed chemo-migration. Taken together, our results revealed that mahanine can be a potential chemotherapeutic agent with efficacy to reduce the concentration of toxic 5-FU in colon cancer.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Antineoplastic Agents / toxicity
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Apoptosis / drug effects
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Carbazoles / pharmacology*
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Carcinoma / drug therapy
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Carcinoma / genetics
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Carcinoma / metabolism
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Carcinoma / physiopathology*
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Cell Line, Tumor
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Colonic Neoplasms / drug therapy
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / physiopathology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Drug Combinations
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Drug Synergism
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Fluorouracil / toxicity*
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Humans
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Murraya / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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Plant Extracts / pharmacology
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Reactive Oxygen Species / metabolism*
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Rutaceae / chemistry
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Tumor Protein p73
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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Antineoplastic Agents
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Carbazoles
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DNA-Binding Proteins
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Drug Combinations
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Nuclear Proteins
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Plant Extracts
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Reactive Oxygen Species
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TP73 protein, human
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Tumor Protein p73
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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mahanine
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PTEN Phosphohydrolase
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PTEN protein, human
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Fluorouracil