Aloe‐Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR‐15a/miR‐16‐1 That Suppresses BCL2

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.

Molecular mechanisms and associated cell signalling pathways underlying the anticancer properties of phytochemical compounds from Aloe species (Review)

“…Aloe-emodin was reported to specifically inhibit MCF-10AT and MCF-7 cell growth, but did not exert any toxicity against the human non-tumorigenic spontaneously immortalised breast epithelial cell line MCF-10A (52). Furthermore, administration of aloe-emodin did not result in any cytotoxicity towards human peripheral mononuclear cells at all concentrations tested in the 0.001-100 µM range, whilst the IC 50 values of aloe-emodin towards the lymphoblastic leukaemia cell line CCRF-CEM, the human colorectal carcinoma cell line HCT116, U87MG, the human breast adenocarcinoma MDA-MB-231 cell line and the tumorigenic human cell line 293T were in the 9.8-22.3 µM range (102).…”

The Chinese Herbal Formula Ruyan Neixiao Cream Inhibits Angiogenesis of Precancerous Breast Lesions via Regulation of Ras/Raf/MEK/ERK Signaling Pathway

“… 15 , 16 Aloe emodin can induce apoptosis of MCF-10AT and MCF-7 cells by up-regulating miR-15a/miR-16-1 of Bcl-2. 33 Acetyl-11-keto-β-boswellic acid can inhibit the expression of ER-α protein through LINC00707/miR-206, thus promoting the apoptosis of MCF-10AT cells and inducing the cell cycle arrest of GO/G1 phase. Boswellic acid can be used as an effective anticancer drug, affecting angiogenesis (VEGF), inflammation (TNF-α, IL-12), apoptosis (caspase-3, caspase-9) and antioxidants (SOD and CAT), thus inhibiting the proliferation of MCF-7 cells and enhancing VEGF antibody induced cell death.…”

Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Qingdu Decoction against Chronic Liver Injury

“…Rhein was reported to protect liver cells from methotrexate-induced injury through modulating apoptosis-related proteins, such as caspase-3 and Bcl-2 family [ 22 ]. On the contrary, some studies reported that all the above compounds could induce apoptosis in many cancer models with different doses [ 23 – 25 ]. Therefore, future studies should explore the differences in drug targets and involve discussion about the relationship between dose and bidirectional effect.…”