Abstract
BackgroundThe incidence and mortality of breast cancer in women is increasing worldwide. Breast cancer contains a subpopulation of cells known as cancer stem cells (CSCs). The CSCs are believed to be responsible for chemotherapeutic resistance and are also involved in tumor initiation, progression, evolution, and metastasis to distant sites. The present study aimed to investigate the anti-CSC potential of selected Ethiopian medicinal plants traditionally used for breast cancer treatment.MethodsThe solvent fractions of three medicinal plants (the ethyl acetate fraction of Vernonia leopoldi, the aqueous fraction of Sideroxylon oxyacanthum, and the chloroform fraction of Clematis simensis) resulting from the methanolic crude extracts were selected based on their previously demonstrated cytotoxic effects on breast cancer cell lines. The effect of these solvent fractions on the status of the cancer stem cell subpopulation of the JIMT-1 cell line was assessed by flow cytometric evaluation of the proportion of aldehyde dehydrogenase positive cells and by measuring colony forming efficiency in a serum-free soft agar assay after treatment. Effects on cell migration using a wound healing assay and on tumor necrosis factor-α-induced translocation of nuclear factor-kappa B to the cell nucleus were also investigated.ResultsThe solvent fractions showed a dose-dependent reduction in the aldehyde dehydrogenase positive subpopulation of JIMT-1 cells. The chloroform fraction of C. simensis (80 μg/mL) completely blocked colony formation of JIMT-1 cells. The wound healing assay showed that all fractions significantly reduced cell migration. The ethyl acetate fraction of V. leopoldi (0.87 μg/mL) significantly inhibited tumor necrosis factor-α-induced nuclear factor-kappa B translocation to the nucleus.ConclusionThe solvent fractions of the medicinal plants showed desirable activities against breast cancer stem cells in the JIMT-1 cell line, which warrants further studies.
Highlights
The incidence and mortality of breast cancer in women is increasing worldwide
Here we investigate the effects of the ethyl acetate fraction of V. leopoldi, the aqueous fraction of S. oxyacanthum, and the chloroform fraction of C. simensis on cancer stem cells (CSCs) properties of the JIMT-1 breast cancer cell line
Treatment with solvent fractions of S. oxyacanthum (SO:2 and SO:3), C. simensis (CS:1 and CS:2) and V. leopoldi VL:1 and VL:2) significantly reduced Colony forming efficiency (CFE) in a dose-dependent manner compared to the controls (Fig. 1b)
Summary
The incidence and mortality of breast cancer in women is increasing worldwide. Breast cancer contains a subpopulation of cells known as cancer stem cells (CSCs). Breast cancer is the most commonly diagnosed malignancy in women worldwide, with an estimated 2.09 million new cases reported in 2018 [1]. It affects approximately 25% of women in both the developed and less developed world [2, 3]. NF-κB is found in the cytoplasm in an inactive form associated with the inhibitor of NF-κB (IκB) [16] When it is released from the inhibitor, p65/NF-κB is translocated to the nucleus and activates gene transcription by binding to sequence-specific targets in DNA [17]. It is an important target for screening potential anticancer agents
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