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01.01.2014 | Research Article

Effects of ellipticine on ALDH1A1-expressing breast cancer stem cells—an in vitro and in silico study

verfasst von: Santhi Latha Pandrangi, Rajasekhar Chikati, Pradeep Singh Chauhan, Chitta Suresh Kumar, Anropa Banarji, Sunita Saxena

Erschienen in: Tumor Biology | Ausgabe 1/2014

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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.

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Titel: Effects of ellipticine on ALDH1A1-expressing breast cancer stem cells—an in vitro and in silico study
verfasst von: Santhi Latha Pandrangi
Rajasekhar Chikati
Pradeep Singh Chauhan
Chitta Suresh Kumar
Anropa Banarji
Sunita Saxena
Publikationsdatum: 01.01.2014
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 1/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-013-1099-y

Springer Medizin

Effects of ellipticine on ALDH1A1-expressing breast cancer stem cells—an in vitro and in silico study

Abstract

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Springer Medizin

Abstract

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