Targets and Mechanism Used by Cinnamaldehyde, the Main Active Ingredient in Cinnamon, in the Treatment of Breast Cancer

Abstract

Background: Breast cancer has become one of the most common malignant tumors in women owing to its increasing incidence each year. Clinical studies have shown that Cinnamomum cassia (L.) J. Presl (cinnamon) has a positive influence on the prevention and treatment of breast cancer.Aim: We aimed to screen the potential targets of cinnamon in the treatment of breast cancer through network pharmacology and explore its potential therapeutic mechanism through cell experiments.Methods: We used the TCMSP, TCM Database @ Taiwan, and TCMID websites and established the active ingredient and target database of cinnamon. Thereafter, we used the GeneCards and OMIM databases to establish a breast cancer-related target database, which matched the cinnamon target database. Based on the matching results, the STRING database was used to analyze the interaction between the targets, and the biological information annotation database was used to analyze the biological process of the target (gene ontology) and the pathway enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG). After establishing the layout of the analysis, we used Cytoscape 3.6.0 software for network analysis. Finally, the cell experiment was used to verify the anti-breast cancer effect of cinnamaldehyde.Results: Our research showed that the main components of cinnamon, including cinnamaldehyde, can play a role in the treatment of breast cancer through 59 possible important targets. Subsequently, enrichment analysis by gene ontology and Kyoto Encyclopedia of Genes and Genomes showed that 83 cell biological processes and 37 pathways were associated with breast cancer (p < 0.05), including the peroxisome proliferator-activated receptor and PI3K-Akt pathway, which are closely related to tumor cell apoptosis. In vitro cell verification experiments showed that cinnamaldehyde can significantly inhibit cell proliferation, change cell morphology, inhibit cell migration and invasion ability, and promote cell apoptosis.Conclusion: Our results showed that cinnamaldehyde is a potential novel drug for the treatment and prevention of breast cancer.

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway

“… Nour et al (2018 ), Abdelmageed et al (2019 ), and Wang et al (2020 ) also found that CA not only reduces atherosclerosis induced by high-cholesterol diet in rabbits but also has therapeutic potential for diabetes mellitus. A number of studies have identified that CA inhibited the proliferation and metastasis of cancers ( Li et al, 2016 ; Wu et al, 2019 ; Liu et al, 2020 ). Liu et al (2020) reported that CA inhibited the proliferation and invasion of breast cancer, and the PI3K/AKT signaling pathway is its potential target through KEGG analysis.…”

“…A number of studies have identified that CA inhibited the proliferation and metastasis of cancers ( Li et al, 2016 ; Wu et al, 2019 ; Liu et al, 2020 ). Liu et al (2020) reported that CA inhibited the proliferation and invasion of breast cancer, and the PI3K/AKT signaling pathway is its potential target through KEGG analysis. Li et al (2016) found that CA reduced the expression level of MMPs, the key proteins that downregulated cell adhesion ability in colorectal cancer cells.…”

“…Among them, the PI3K/AKT signaling pathway is the most frequently activated pathway ( Ediriweera et al, 2019 ; Zhang et al, 2019 ; Nguyen et al, 2019 ), which is also involved in regulating cell proliferation, apoptosis, invasion, survival, and angiogenesis ( Shao et al, 2020 ). Liu et al (2020) used GeneCards and OMIM databases for the enrichment analysis and found that CA is closely related to the AKT/PI3K signaling pathway in breast cancer. Liu and Huang confirmed that CA regulated colorectal cancer and osteosarcoma progressing via the AKT/PI3K signaling pathway ( Li et al, 2016 ; Huang et al, 2020 ).…”

“…For example, CA acts in synergy with oxaliplatin to reverse nodal hypoxia-induced EMT by inhibiting the Wnt/β-catenin pathway and exerting anti-tumor effects in colorectal cancer ( Wu et al, 2019 ). Liu et al (2020 ) identified the antioxidant effects of CA in breast cancer and could inhibit cell growth and promote apoptosis through PI3K/AKT and NF-κB pathways. However, the role of CA in the treatment of ovarian cancer is still unclear.…”

Anti-proliferative and immunomodulatory potencies of cinnamon oil on Ehrlich ascites carcinoma bearing mice

“…The main compound in the cinnamon oil is cinnamaldehyde 18 , 19 . Cinnamaldehyde or transcinnamaldehyde is known by its antimicrobial, antipyretic and anti-inflammatory potencies 18 , also it exert anticancer activities via controlling tumor cell growth, proliferation capabilities, inducing apoptosis and necrosis of tumor cells 19 , 20 . Another active ingredients of cinnamon oil are eugenol and cinnamic acid which are known by their antitumorgenesis role through inducing tumor cell apoptosis and exerting antioxidative properties 14 , 21 , 22 .…”