Cinnamon oil as a co-chemotherapy agent through inhibition of cell migration and MMP-9 expression on 4T1 cells

Alma Nuril Aliyah; Ghina Lintangsari; Gergorius Gena Maran; Adam Hermawan; Edy Meiyanto

doi:10.1515/jcim-2020-0165

Article

Cinnamon oil as a co-chemotherapy agent through inhibition of cell migration and MMP-9 expression on 4T1 cells

Alma Nuril Aliyah , Ghina Lintangsari , Gergorius Gena Maran , Adam Hermawan and Edy Meiyanto

Published/Copyright: June 15, 2021

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From the journal Journal of Complementary and Integrative Medicine Volume 19 Issue 4

Abstract

Objectives

The long-term and high-dose use of doxorubicin as chemotherapy for triple-negative breast cancer (TNBC) patients induces epithelial-to-mesenchymal transition (EMT) and stimulates cancer metastasis. Cinnamaldehyde is a major compound of cinnamon oil (CO) suppressing Snail and NFκB activity that are involved in cell migration. This study aims to explore the activity of CO as a co-chemotherapeutic agent on 4T1 breast cancer cells.

Methods

The CO was obtained by water and steam distillation and was characterized phytochemically by gas chromatography-mass spectrometry (GC-MS). Cytotoxic activity of single CO or in combination with doxorubicin was observed by MTT assay. Cell migration and MMP-9 expression were measured by scratch wound healing and gelatin zymography assays. The intracellular reactive oxygen species (ROS) levels were observed by 2′,7′–dichlorofluorescin diacetate (DCFDA) staining flowcytometry.

Results

The phytochemical analysis with GC-MS showed that CO contains 14 compounds with cinnamaldehyde as the major compound. CO exhibited cytotoxicity on 4T1 cells with the IC₅₀ value of 25 μg/mL and its combination with doxorubicin decreased cell viability and inhibited cell migration compared to a single use. Furthermore, the combination of CO and doxorubicin inhibited MMP-9 expression and elevated intracellular ROS levels compared to control.

Conclusions

CO has the potential to be developed as a co-chemotherapy agent through inhibition of cell migration, and intracellular ROS levels elevation.

Keywords: 4T1 cells; cell migration; cinnamon oil; co-chemotherapy; doxorubicin

Corresponding author: Adam Hermawan, Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, 55281 Yogyakarta, Indonesia; and Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, 55281 Yogyakarta, Indonesia, E-mail: adam_apt@ugm.ac.id

Funding source: Universitas Gadjah Mada

Acknowledgments

The authors thank Badan Penerbit dan Publikasi (BPP) Universitas Gadjah Mada (UGM) and Ms. Sarassati Nur Miawati for their writing assistance.

Research funding: Final Project Recognition, Universitas Gadjah Mada, Indonesia, contract no. 2129/UN1/DITLIT/DIT-LIT/LT/2019.
Author contributions: ANA: data acquisition, analysis and writing the manuscript. GL and GGM: data acquisition. EM: conception of study design and writing the manuscript. AH: conception of study design, funding acquisition, data analysis and writing the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: Not applicable.

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Received: 2020-05-17

Accepted: 2021-05-26

Published Online: 2021-06-15

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Articles in the same Issue

https://doi.org/10.1515/jcim-2020-0165

Keywords for this article

4T1 cells; cell migration; cinnamon oil; co-chemotherapy; doxorubicin