Improved chemosensitivity in cervical cancer to cisplatin: synergistic activity of mahanine through STAT3 inhibition.
Toxicity reduction of cisplatin is necessary for improved treatment of cancer. Here we have demonstrated the synergistic growth-inhibitory effect of cisplatin on cervical cancer cells in-combination with a nontoxic herbal carbazole alkaloid, mahanine. Mahanine enhanced cisplatin-induced apoptosis and reduced its effective concentration ∼5-8 folds. Mahanine inhibited JAK1 and Src and subsequently promoted proteasome-mediated degradation of STAT3. This event was further enhanced in-combination with cisplatin and subsequently inhibited cancer cell migration. Collectively, our results revealed that mahanine may be a prospective agent to reduce the concentration of cisplatin in adjunct for the treatment of cancer and thereby decreasing its toxicity.
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
Ranjita
R
Das
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
Kaushik
K
Bhattacharya
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
Suman K
SK
Samanta
National Institute of Pharmaceutical Education and Research, Kolkata, India.
Bikas C
BC
Pal
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India. Electronic address: cmandal@iicb.res.in.
Chitra
C
Mandal
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002227:Carbazoles / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D002227:Carbazoles; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C465290:mahanine; D002945:Cisplatin
Cervical cancer; Cisplatin; Mahanine; STAT3; Synergism