Abstract
Resveratrol (RSV) is known to possess anticancer properties in many types of cancers like breast cancer, in which POLD1 may serve as a potential target. However, the anticancer mechanism of RSV on triple negative breast cancer (TNBC) remains unclear. In the present study, the antitumor effects and mechanism of RSV on TNBC cells were analyzed by RNA sequencing (RNA-seq), which was then verified via cell counting kit-8 (CCK8), immunofluorescence, immunohistochemistry, Western Blot (WB), flow cytometry, and hematoxylin-eosin (HE) staining. According to the corresponding findings, the survival rate of MDA-MB-231 cells gradually decreased as RSV treatment concentration increased. The RNA-seq analysis results demonstrated that genes affected by RSV treatment were mainly involved in apoptosis and the p53 signaling pathway. Moreover, apoptosis of MDA-MB-231 cells induced by RSV was observed to be mainly mediated by POLD1. When treated with RSV, the expression levels of full length PARP1, PCNA, and BCL-2 were found to be significantly reduced, and the expression level of Cleaved-PARP1 as well as Cleaved-Caspase3 increased significantly. Additionally, the mRNA expression of POLD1 was significantly reduced after treatment with RSV, and the protein expression level was also inhibited by RSV in a concentration-dependent manner. The prediction of domain interaction suggested that RSV may bind to at least five functional domains of the POLD1 protein (6s1m, 6s1n, 6s1o, 6tny and 6tnz). Furthermore, after RSV treatment, the anti-apoptotic index (PCNA, BCL-2) of MDA-MB-231 cells was found to decrease while the apoptosis index (caspase3) increased. Moreover, the overexpression of POLD1 reduced the extent of apoptosis observed in MDA-MB-231 cells following RSV treatment. Moreover, animal experimental results showed that RSV had a significant inhibitory effect on the growth of live tumors, while POLD1 overexpression was shown to antagonize this inhibitory effect. Accordingly, this study’s findings reveal that RSV may promote the apoptosis of TNBC cells by reducing the expression of POLD1 to activate the apoptotic pathway, which may serve as a potential therapy for the treatment of TNBC.
Highlights
In 2018, there were about 2.1 million newly diagnosed female breast cancer cases globally, accounting for nearly a quarter of all female cancer cases [1]
triple negative breast cancer (TNBC) accounts for about 15% - 20% of breast cancer [4], and compared to hormonal receptor positive or HER2 positive diseases, TNBC is characterized by its highly aggressive clinical progression due to its earlier onset age, greater metastatic potential and worse clinical results [5, 6]
By comparing cells treated with different concentrations of RSV at 24 h, 36 h, and 48 h, a significant difference was found between the relative survival rate of TNBC cells (Figure 2C)
Summary
In 2018, there were about 2.1 million newly diagnosed female breast cancer cases globally, accounting for nearly a quarter of all female cancer cases [1]. TNBC accounts for about 15% - 20% of breast cancer [4], and compared to hormonal receptor positive or HER2 positive diseases, TNBC is characterized by its highly aggressive clinical progression due to its earlier onset age, greater metastatic potential and worse clinical results [5, 6]. TNBC progresses very rapidly, and due to the lack of common therapeutic targets, current methods in controlling disease development are very limited [7]. Several studies have shown that resveratrol (RSV) possesses anticancer properties [9] in breast cancer [10] and may serve as a potential therapeutic candidate for TNBC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
