Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Formononetin promotes apoptosis of colorectal cancer cells via activation of mitochondria-dependent MAPK pathway

Xiao-hong Wang¹, Zhi-guang Sun² , Lei Luo³, Li-na Liu⁴, Jing Yan⁵, Li Xuan⁶

¹Department of Gastroenterology, Xuzhou Affiliated Hospital of Nanjing University of Chinese Medicine; ²Department of Headmaster's Office, Nanjing University of Chinese Medicine; ³Department of Gastroenterology, Second Affiliated Hospital of Nanjing University of Chinese Medicine; ⁴Department of Hepatology, The Affiliated Hospital of Nanjing University of Chinese Medicine; ⁵Department of Research and Experiment Center, First Clinical Medical College, Nanjing University of Chinese Medicine; ⁶Department of Gastroenterology, Xuzhou Hospital of Traditional Chinese Medicine, Nanjing, China.

For correspondence:- Zhi-guang Sun Email: ZhiguangSunasd@163.com

Accepted: 22 January 2019 Published: 28 February 2019

Citation: Wang X, Sun Z, Luo L, Liu L, Yan J, Xuan L. Formononetin promotes apoptosis of colorectal cancer cells via activation of mitochondria-dependent MAPK pathway. Trop J Pharm Res 2019; 18(2):243-249 doi: 10.4314/tjpr.v18i2.4

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate whether formononetin exhibits antitumor activity in colorectal cancer cell lines via the mitochondria-dependent mitogen-activated protein kinase (MAPK) pathway.

Methods: Human colorectal cells were treated with various doses of formononetin for 24 h, followed by Cell Counting Kit-8 (CCK-8) assay and western blot. Human colorectal cells were incubated with equivalent vehicle (DMSO) or 100 µM formononetin for 24 h, followed by nuclear staining with propidium iodide (PI) and diamidino-2-phenylindole (DAPI) for analyses of apoptosis. Human colorectal cells were incubated with equivalent vehicle or 100 µM formononetin for 24 h followed by analysis of cell migration and invasion. Human colorectal cells were incubated with equivalent vehicle (DMSO) or 100 µM formononetin for various duration (3, 6, 12, and 24 h), followed by detection of intracellular reactive oxygen species (ROS) level and measurement of mitochondrial membrane potential (Δψm) to monitor mitochondria functionality.

Results: In human colorectal cancer cell lines SW1463 and T84, formononetin (> 20 µM) significantly inhibited cell growth (p < 0.05) in a dose-dependent manner, noticeably induced apoptosis, and suppressed cell migration and invasion. Western blot analysis revealed that formononetin treatment caused significantly increased levels of proapoptotic proteins, and suppression of cell proliferation-related protein and matrix metallopeptidases (MMP) levels. Formononetin also induced mitochondrial depolarization and ROS generation in a time-dependent manner, indicating that formononetin mediates human colorectal cancer cell apoptosis via activation of MAPK pathway in a dose-dependent manner.

Conclusion: Formononetin induces human colorectal cancer cell apoptosis via mitochondria-dependent MAPK pathway, thus lending experimental support for the clinical application of formononetin for colorectal cancer therapy.

Keywords: Formononetin, Colorectal cancer, Mitochondria, Reactive oxygen species, Cytochrome C, Mitogen-activated protein kinase