Abstract
Purpose Aloe-emodin (AE) is a natural compound derived from aloe vera and palmatum rhubarb and shows anticancer activities in various cancers. Bcl-2 family is the main regulator of cell death or cell survival. This study describes the effects of AE on proliferation of breast tumor (BT) cells. Methods MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 cell lines were exposed to AE. Cell proliferation and apoptosis were assessed by CCK-8 and flow cytometry. Protein levels were measured by Western blotting. The levels of mRNA and miRNA were examined by RT-PCR. Bioinformatics was applied to screen miRNAs that bind to 3′-UTR of mRNA. Results The results showed that AE selective activity inhibited the proliferation and induced apoptosis of MCF-10AT and MCF-7 cells but exhibited no significant inhibition in MCF10A and MDA-MB-231 cells. Mechanistically, AE dose-dependently decreased the protein expression of Bcl-2 and Bcl-xl, while it increased Bax protein expression in MCF-10AT and MCF-7 cells. The levels of Bcl-xl and Bax mRNA were altered by AE treatment, which was consistent with the protein expression results. However, Bcl-2 mRNA levels were not affected in either cell line, suggesting that AE may modulate the protein translation of Bcl-2 through miRNAs. In all candidate miRNAs that bind to 3′-UTR of Bcl-2, miR-15a and miR-16-1 were dose-dependently downregulated by AE. Moreover, inhibition of miR-15a/16-1 could eliminate the inhibition of MCF-10AT and MCF-7 cells growth by AE and could reverse the downregulation of AE-induced Bcl-2 protein level. Conclusion Our research provides an important basis that AE induces BT cell apoptosis through upregulation of miR-15a/miR-16-1 that suppresses BCL2.
Highlights
Breast cancer (BC) is a type of molecular heterogeneous cancer, which is the most frequently diagnosed malignancy in women and the leading cause of cancer death in women worldwide
AE Dose-Dependently Suppresses breast tumor (BT) Cell Proliferation. e effects of AE (20, 40, 60, 80, and 100 μM) on cell proliferation were examined in MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 cell lines using the Cell Counting Kit-8 (CCK-8) assay
MCF-10AT and MCF-7 cells were treated with PBS and AE (20 or 40 μM) for 72 h and the percentage of apoptosis cells was measured by Annexin V/Propidium Iodide (PI) staining assay
Summary
Breast cancer (BC) is a type of molecular heterogeneous cancer, which is the most frequently diagnosed malignancy in women and the leading cause of cancer death in women worldwide. By directly binding CCND1 3′-UTR, miR-15a and miR-16-1 inhibited CCND1 transcription, inducing apoptosis and cell cycle arrest in osteosarcoma [10]. MiR-15/ 16 play a vital part in the coordination and regulation of early differentiation of tumor cell proliferation, survival, and memory. Studies have shown that AE has antiproliferation effects and induces apoptosis [15]; it can inhibit cell proliferation in SW620 and HT29 colorectal cancer cell lines [16, 17]. Whether AE can inhibit the expression of Bcl-2 by upregulating the expression of miR-15/16 in BT cells and induce apoptosis is unclear. We investigate the inhibition of AE on BTcells and the effect of miR-15a/16-1 on the cell apoptosis of BT with AE treatment. The downregulation of Bcl-2 protein and upregulation of miR-15a/16-1 may be related to AE-induced apoptosis
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