mahanine and Colonic-Neoplasms

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.

Topics: Antineoplastic Agents; Apoptosis; Carbazoles; Carcinoma; Cell Line, Tumor; Colonic Neoplasms; DNA-Binding Proteins; Drug Combinations; Drug Synergism; Fluorouracil; Humans; Murraya; Nuclear Proteins; Plant Extracts; PTEN Phosphohydrolase; Reactive Oxygen Species; Rutaceae; Tumor Protein p73; Tumor Suppressor Protein p53; Tumor Suppressor Proteins