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. 2020 Dec 9:11:582719.
doi: 10.3389/fphar.2020.582719. eCollection 2020.

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

Yufei Liu  1 , Tian An  2 , Donggui Wan  3 , Bowen Yu  1 , Yingyi Fan  1 , Xiaohua Pei  1   4
Affiliations

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

Yufei Liu et al. Front Pharmacol. .

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.

Keywords: MDA-MB-231; active components; breast cancer; cinnamaldehyde; network pharmacology.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Cinnamon-compounds-breast cancer network. (A) Cinnamon-compounds, (B) Cinnamon-related compounds-breast cancer. Yellow represents the main compound in cinnamon and blue represents the target associated with breast cancer.
FIGURE 2
FIGURE 2
Venn diagram of the targets in breast cancer and cinnamon.
FIGURE 3
FIGURE 3
PPI network of 59 nodes. A total of 59 overlapped target genes were used to construct the PPI network.
FIGURE 4
FIGURE 4
Core target of cinnamon for the treatment of breast cancer.
FIGURE 5
FIGURE 5
Top 20 GO terms and KEGG pathways. (A) GO biological process analysis, (B) KEGG pathway analysis.
FIGURE 6
FIGURE 6
Rate of inhibition of MDA-MB-231 cell proliferation and the IC50 of cinnamaldehyde. CA, cinnamaldehyde.
FIGURE 7
FIGURE 7
Cell morphological and cytoplasmic changes in MDA-MB-231 cells in the different treatment groups. (A) Cell morphological changes of MDA-MB-231 cells in different treatment groups (original magnification, ×100); (B) Hoechst 33,258 staining shows changes in the cytoplasm of MDA-MB-231 cells in different cinnamaldehyde treatment groups (original magnification, ×200). CA, cinnamaldehyde.
FIGURE 8
FIGURE 8
Comparison of the apoptotic rate of MDA-MB-231 cells administered different concentrations of cinnamaldehyde by Annexin V-FITC and PI double staining. (A)–(E) shows the cell apoptotic rate in the cinnamaldehyde groups administered different concentrations of cinnamaldehyde (∗∗∗compared to the control group p < 0.001). CA, cinnamaldehyde.
FIGURE 9
FIGURE 9
Effects of different concentrations of cinnamaldehyde on the migration and invasion ability of MDA-MB-231 cells after a 48-h intervention. (A), (B), Wound healing assay of MDA-MB-231 cells in different treatment groups (original magnification, ×100). (C), (D), Invasive assay after 48 h of CA intervention (original magnification, ×200) (∗, ∗∗, ∗∗∗, ∗∗∗∗ compared to the control group p < 0.05, p < 0.01, p < 0.001, and p < 0.0001, respectively). CA, cinnamaldehyde.
FIGURE 10
FIGURE 10
Overall framework of cinnamaldehyde for the treatment of breast cancer. Through the network pharmacological integration strategy, cinnamaldehyde (the main chemical component of cinnamon in breast cancer) was selected. Based on in vitro cell experiments, cinnamaldehyde was confirmed to promote the apoptosis of breast cancer tumor cells and inhibit cell migration and invasion.
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References

    1. Blucher C., Iberl S., Schwagarus N. (2020). Secreted factors from adipose tissue reprogram tumor lipid metabolism and induce motility by modulating PPARα/ANGPTL4 and FAK [published online ahead of print, 2020 Aug 28]. Mol. Cancer Res. 1223, 2019 10.1158/1541-7786.MCR-19-1223 - DOI - PubMed
    1. Bray F., Ferlay J., Soerjomataram I. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 9(12), 24–28. 10.3322/caac.21492 - DOI - PubMed
    1. Buglak N. E., Jiang W., Bahnson E. S. M. (2018). Cinnamic aldehyde inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in Zucker Diabetic Fatty rats. Redox Biol. 19, 166–178. 10.1016/j.redox.2018.08.013 - DOI - PMC - PubMed
    1. Cabello C. M., Bair W. B., 3rd, Lamore S. D. (2009). The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth. Free Radic. Biol. Med. 46(2), 220–231. 10.1016/j.freeradbiomed.2008.10.025 - DOI - PMC - PubMed
    1. Cai M., Liang X., Sun X. (2019). Nuclear receptor Coactivator 2 promotes human breast cancer cell growth by positively regulating the MAPK/ERK pathway. Front Oncol. 9, 164 10.3389/fonc.2019.00164 - DOI - PMC - PubMed