Khat promotes human breast cancer MDA-MB-231 cell apoptosis via mitochondria and MAPK-associated pathways

Lu,Yu; Li,Yanyan; Xiang,Min; Zhou,Jie; Chen,Juan

doi:10.3892/ol.2017.6708

Khat promotes human breast cancer MDA-MB-231 cell apoptosis via mitochondria and MAPK-associated pathways

Authors:
- Yu Lu
- Yanyan Li
- Min Xiang
- Jie Zhou
- Juan Chen
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Affiliations: Department of Endocrinology, Taizhou People's Hospital, Nantong University, Taizhou, Jiangsu 225300, P.R. China, Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: August 2, 2017 https://doi.org/10.3892/ol.2017.6708
Pages: 3947-3952
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Khat (Catha edulis Forsk) is a flowering evergreen plant in Eastern Africa and Southwestern Arabia. Consumption of Khat has been associated with the development of oral cancer, but its mechanism of action on the molecular level remains unclear. The present study demonstrated the cytotoxic effect of khat extracts on the human breast cancer cell line MDA‑MB‑231. Trypan blue exclusion assays, flow cytometry, fluorescent and electron microscopy, as well as western blotting were used to analyze the effects of Khat on the cell viability of breast cancer cells, expression of apoptotic‑associated proteins and the levels of reactive oxygen species (ROS). The results of the present study demonstrated that treatment with 400 µg/ml khat was able to induce cell death in breast cancers, with an increase in the protein expression of apoptosis regulator Bax and a decrease in the expression of B‑cell lymphoma 2, along with a decrease in ROS levels in a time‑dependent manner. Furthermore, the expression of activated c‑Jun N‑terminal and extracellular regulated protein kinases was increased in khat‑treated cells compared with untreated cells. Mitochondria participated in cell apoptosis through the release of apoptogenic proteins to the cytosol and the generation of excess reactive oxygen species. The results of the present study suggest that khat induces MDA‑MB‑231 cell apoptosis via MAPK activation and mitochondrial-mediated death.

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