1. Resensitization of Akt Induced Docetaxel Resistance in Breast Cancer by 'Iturin A' a Lipopeptide Molecule from Marine Bacteria Bacillus megaterium.
- Author
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Dey G, Bharti R, Das AK, Sen R, and Mandal M
- Subjects
- Antifungal Agents pharmacology, Antineoplastic Agents pharmacology, Apoptosis drug effects, Apoptosis Regulatory Proteins metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, Female, Gene Expression Regulation, Neoplastic, Humans, Signal Transduction, Tumor Cells, Cultured, Bacillus megaterium chemistry, Breast Neoplasms drug therapy, Docetaxel pharmacology, Drug Resistance, Neoplasm drug effects, Lipopeptides pharmacology, Peptides, Cyclic pharmacology, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Development of the resistance is the major problem in cancer therapy. Docetaxel is a taxol alkaloid that is frequently used in metastatic breast cancer. However, resistance often limits the usefulness of this drug in many breast cancer patients. Manipulation of resistant cells to re-sensitize to the therapeutic effect of docetaxel is current strategy to overcome this problem. Here, we have introduced 'Iturin A' as a potent chemosensitizer in docetaxel resistant breast cancer cells. Combination of Iturin A and docetaxel treatment significantly hampered the proliferation of docetaxel resistant MDA-MB-231 and MDA-MB-468 breast cancer cells. Cell cycle analysis also showed massive amount of apoptotic population (Sub G0/G1) in combination therapy. A number of apoptotic and anti-apoptotic proteins were significantly altered in dual drug treated groups. Caspase 3 dependent cell death was observed in dual treatment. Molecular mechanism study showed that over-expression of Akt and its downstream signaling pathway was associated with docetaxel resistance. Iturin A significantly reduced Akt signaling pathway in resistant cells. This mechanistic action might be the reason behind the chemo-sensitization effect of Iturin A in docetaxel resistant breast cancer cells. In conclusion, Iturin A resensitized the resistant breast cancer cells to docetaxel therapy by inhibiting Akt activity.
- Published
- 2017
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