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

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.

Transcriptome and proteome analysis reveals the anti-cancer properties of Hypnea musciformis marine macroalga extract in liver and intestinal cancer cells

“…Induction of apoptosis in both cancer cell lines was also confirmed by Annexin V detection using flow cytometry analysis. As known, apoptosis is one of the major chemopreventive mechanisms of natural products [ 48 ]. Although HME-induced significant apoptosis in both cancer cell lines, apoptotic cells were not the majority of total cells at any time point of treatment, suggesting that HME may induce cancer cell death through apoptosis along with other programmed cell death forms (e.g., ferroptosis, necroptosis and pyroptosis) or autophagy.…”

Αnti-prion effects of anthocyanins

“…1 ) [ 33 ]. Due to their potent anti-oxidant action, ACNs have been extensively tested as potential remedies against oxidative stress associated conditions, such as cancer [ [34] , [35] , [36] , [37] ], cardiovascular diseases [ [38] , [39] , [40] , [41] ] and neurodegeneration [ [42] , [43] , [44] , [45] ]. Importantly, their ability to penetrate the Blood-Brain Barrier (BBB) renders them exceptional neuroprotective compounds [ 46 ].…”

Zero- and Low-Alcohol Fermented Beverages: A Perspective for Non-Conventional Healthy and Sustainable Production from Red Fruits

“…The most common naturally occurring anthocyanins are the 3-O-glycosides or 3,5-di-O-glycosides of cyanidin, delphinidin, peonidin, petunidin, pelargonidin, and malvidin. Numerous studies have shown that they can have various biological activities, including antimicrobial and anti-inflammatory activities, protective action against various degenerative diseases, and an important role in decreasing the invasiveness of tumor cells [13][14][15][16][17]. Nevertheless, the profile and concentration of anthocyanins are different depending on the fruit.…”