Aloe-Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR-15amiR-16-1 That Suppresses BCL2

Abstract EN

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.