Anthocyanins Reduce Cell Invasion and Migration through Akt/mTOR Downregulation and Apoptosis Activation in Triple-Negative Breast Cancer Cells: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Breast cancer is the second most common cancer and the most commonly occurring cancer among women in the world. It is estimated that more than 2 million cases emerged in 2020 and that this number will increase even more in the coming years. More specifically, triple-negative breast cancer (TNBC) accounts for 10–20% of invasive breast cancers and represents a consistent subgroup of breast cancers with heterogeneous clinical presentation, behavior, pathology, and response to treatment. The standard therapy for TNBC patients consists of chemotherapy; however, about 50% of patients develop drug resistance, promoting poor overall survival. Thus, studies have focused on discovering complementary therapeutic options, including the use of anthocyanins. In this sense, the systematic review and meta-analysis can be seen as a powerful tool in the compilation and statistical analysis of data from primary articles to prove the effects promoted by anthocyanins in TNBC cells suggested in the literature. ABSTRACT: Background: Studies have suggested the chemopreventive effects of anthocyanins on breast cancer carcinogenesis. This systematic review and meta-analysis aimed to evaluate the effect of anthocyanins on triple-negative breast cancer cells (TNBC) cultured in vitro. Methods: We searched for all relevant studies that evaluated the mechanisms of migration, invasion, Akt/mTOR and MAPK pathways, and apoptosis, using PubMed and Scopus. Means and standard deviation were used, and a randomized effects model was applied, with a confidence interval of 95%. Statistical heterogeneity between studies was assessed using the Chi2 test and I2 statistics. All analyses were performed using RevMan software (version 5.4). Results: Eleven studies were included in the systematic review and ten in the meta-analysis, where the roles of anthocyanin-enriched extract or cyanidin-3-O-glucoside (C-3-O-G) on MDA-MB-231 and MDA-MB-453 cells were investigated. Discussion: There was a significant reduction in invasion (mean difference: −98.64; 95% CI: −153.98, −43.3; p ˂ 0.00001) and migration (mean difference: −90.13; 95% CI: −130.57, −49.68; p ˂ 0.00001) in TNBC cells after anthocyanins treatment. Anthocyanins also downregulated Akt (mean difference: −0.63; 95% CI: −0.70, −0.57; p ˂ 0.00001) and mTOR (mean difference: −0.93; 95% CI: −1.58, −0.29; p = 0.005), while JNK (mean difference: −0.06; 95% CI: −1.21, 1.09; p = 0.92) and p38 (mean difference: 0.05; 95% CI: −1.32, 1.41; p = 0.95) were not modulated. There was also an increase in cleaved caspase-3 (mean difference: 1.13; 95% CI: 0.11, 2.16; p = 0.03), cleaved caspase-8 (mean difference: 1.64; 95% CI: 0.05, 3.22; p = 0.04), and cleaved PARP (mean difference: 0.93; 95% CI: 0.54, 1.32). Although the difference between control and anthocyanin groups was not significant regarding apoptosis rate (mean difference: 3.63; 95% CI: −2.88, 10.14; p = 0.27), the analysis between subgroups showed that anthocyanins are more favorable in inducing overall apoptosis (p ˂ 0.00001). Conclusion: The results show that anthocyanins hold promise in fighting against TNBC, but their effects should not be generalized. In addition, further primary studies should be conducted so that more accurate conclusions can be drawn.