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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pandrangi, Santhi Latha Chikati, Rajasekhar Chauhan, Pradeep Singh Kumar, Chitta Suresh Banarji, Anropa Saxena, Sunita |
| Description | Country affiliation: India Author Affiliation: Pandrangi SL ( Tumour Biology Laboratory, National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, 110029, India.) |
| Abstract | Targeting breast cancer stem cells (BCSCs) offers a promising strategy for breast cancer treatment. We examined the plant alkaloid ellipticine for its efficacy to inhibit the expression of aldehyde dehydrogenase 1 class A1 (ALDH1A1)-positive BCSCs by in vitro and in silico methods. At 3 mM concentration, ellipticine decreased the expression of ALDH1A1-positive BCSCs by 62% (p = 0.073) in the MCF7 cell line and by 53% (p = 0.024) in the SUM159 cell line compared to vehicle-treated cultures. Ellipticine significantly reduced the formation of mammospheres, whereas paclitaxel enhanced mammosphere formation in both the treated cell lines. Interestingly, when treated with a combination of ellipticine and paclitaxel, the percentage of ALDH1A1-positive BCSCs dropped by several fold in vitro. A homology model of Homo sapiens ALDH1A1 was built using the crystal structure of NAD-bound sheep liver class I aldehyde dehydrogenase [PDB ID: 1BXS] as a template. Molecular simulation and docking studies revealed that the amino acids Asn-117 and Asn-121, Glu-249, Cys-302, and Gln-350, present in the active site of human ALDH1A1, played a vital role in interacting with the drug. The present study suggests that ellipticine reduces the proliferation and self-renewal ability of ALDH1A1-positive BCSCs and can be used in combination with a cytotoxic drug like paclitaxel for potential targeting of BCSCs. |
| File Format | HTM / HTML |
| ISSN | 10104283 |
| Issue Number | 1 |
| Volume Number | 35 |
| e-ISSN | 14230380 |
| Journal | Tumor Biology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2014-01-01 |
| Publisher Place | Netherlands |
| Access Restriction | Subscribed |
| Subject Keyword | Discipline Medicine__semicolon__oncology Aldehyde Dehydrogenase Metabolism Antineoplastic Agents Pharmacology Breast Neoplasms Ellipticines Neoplastic Stem Cells Drug Effects Chemistry Genetics Amino Acid Sequence Catalytic Domain Cell Line, Tumor Cell Proliferation Female Gene Expression Regulation, Neoplastic Humans Mcf-7 Cells Molecular Docking Simulation Molecular Dynamics Simulation Molecular Sequence Data Paclitaxel Protein Binding Protein Conformation Spheroids, Cellular Tumor Cells, Cultured Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |
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