Effects of ellipticine on ALDH1A1-expressing breast cancer stem cells--an in vitro and in silico study
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Updated: May 8, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Santhi Latha Pandrangi1, Rajasekhar Chikati, Pradeep Singh Chauhan
1Tumour 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.
Insights
The plant alkaloid ellipticine effectively targets breast cancer stem cells (BCSCs) expressing ALDH1A1. Combining ellipticine with paclitaxel significantly reduces BCSCs, offering a promising therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Targeting breast cancer stem cells (BCSCs) is crucial for effective cancer treatment.
- Aldehyde dehydrogenase 1 class A1 (ALDH1A1) is a marker for BCSCs.
- Plant-derived compounds are explored for novel cancer therapies.
Purpose of the Study:
- To investigate the efficacy of the plant alkaloid ellipticine in inhibiting ALDH1A1-positive BCSCs.
- To evaluate ellipticine's effect on mammosphere formation.
- To explore the combination therapy of ellipticine and paclitaxel for targeting BCSCs.
Main Methods:
- In vitro studies using MCF7 and SUM159 breast cancer cell lines.
- In silico molecular modeling, simulation, and docking studies of human ALDH1A1.
- Assessment of ALDH1A1 expression and mammosphere formation.
Main Results:
- Ellipticine significantly decreased ALDH1A1-positive BCSCs in both cell lines (62% in MCF7, 53% in SUM159).
- Ellipticine reduced mammosphere formation, while paclitaxel enhanced it.
- Combination therapy with ellipticine and paclitaxel led to a multi-fold decrease in ALDH1A1-positive BCSCs.
Conclusions:
- Ellipticine inhibits the proliferation and self-renewal of ALDH1A1-positive BCSCs.
- Ellipticine shows potential as a therapeutic agent for breast cancer.
- Combination therapy with paclitaxel may enhance the targeting of BCSCs.
