# Resveratrol: A Review on the Biological Activity and Applications
## 3 Antitumor Properties
### Breast Cancer  
Breast cancer (BC) is one of the most prevalent tumors in females and is culpable for the principal cancer-related deaths after lung cancer. The anticancer mechanisms of RSV concerning BC involve the restriction of cell proliferation, decreasing of cell viability, invasion, and metastasis. However, despite its favorable therapeutic effects, it has limitations due to the reduced pharmacokinetics (PK), stability, and poor water solubility, implying the help of nanodelivery systems to enhance its bioavailability [55; 56]. RSV-modified mesoporous silica nanoparticles (NPs) inhibit BC progression more efficiently, in comparison to the phytochemical alone, via suppressing the NF-kB signaling pathway, indicating that they are a novel and more secure method for applying in the complex therapeutics of BC [57].  
Some research involved RSV-loaded solid lipid NPs that were properly designed to improve BC cells. The NPs presented a higher capacity than free RSV in suppressing the proliferation of tumor cells and displayed much better inhibitory actions on the incursion and migration of BC cells [58; 59]. Additional data, important in the BC applications, established that transferrin-cathepsin B cleavable peptide-modified mesoporous silica NPs encapsulated RSV substantially reduced cell viability and enhanced cell apoptosis [60].  
Research has shown that RSV activates the transcription of cytochrome P450 CYP1A1 and reduces the formation of carcinogen-induced preneoplastic lesions in mouse mammary tissues. It also prevents the growth of mouse skin tumors in two-stage models, inhibits the enzymatic actions of COX-1 and COX-2 in cell-free experiments, and blocks COX-2 mRNA along with the activation of protein kinase C (PKC) and activator protein-1 (AP-1)-mediated gene expressions in mammary epithelial cells [61].  
A possible mechanism by which RSV could control the cell cycle and apoptosis has been investigated, exploring the human BC MCF-7 cell line. The results showed a dose-dependent anti-proliferative effect of RSV that was correlated with a notable inhibition of cyclin D and cyclin-dependent kinase (CDK)4 proteins and stimulation of p53 and CDK inhibitor p21 WAF1/CIP [62; 63]. Apoptosis caused by RSV was determined to happen exclusively in BC cells exhibiting wild-type p53 but not in mutant p53-expressing cells [64].  
The growth factor heregulin-beta1 (HRG-\(\beta\)1) promotes the tumorigenicity and metastasis of human BC cells. MMP-9 is a crucial enzyme in the degeneration of extracellular matrices and has an altered expression in BC infiltration and metastasis. RSV showed anti-carcinogenic activities in both in vitro and in vivo explorations that imply it suppresses the MMP-9 expression in BC cells, connected with the downregulation of the mitogen-activated protein kinase (MAPK)/ERK signaling pathway [65].  
Metastasis is an important cause of decease in patients with BC. In the evolution of the tumor, epithelial-mesenchymal transition (EMT) is essential to supporting the invasion and migration of cancer cells. RSV suppresses the migration of human BC cells by invalidating the transforming growth factor-beta1 (TGF-\(\beta\)1)-induced EMT and inhibits lung metastasis in a xenograft-bearing mouse model [66]. The cytotoxic action of RSV on human BC cells may be correlated with its pro-oxidant effect, which inhibits casein kinase 2 activity, influencing cell viability and mitochondrial function [36; 67].