Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+‑mediated mitochondrial pathway

Xie,Le; Xiang,Guang‑Hong; Tang,Tao; Tang,Yan; Zhao,Ling‑Yun; Liu,Dong; Zhang,You‑Ren; Tang,Jin‑Tian; Zhou,Shen; Wu,Da‑Hua

doi:10.3892/mmr.2016.5784

Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+‑mediated mitochondrial pathway

Authors:
- Le Xie
- Guang‑Hong Xiang
- Tao Tang
- Yan Tang
- Ling‑Yun Zhao
- Dong Liu
- You‑Ren Zhang
- Jin‑Tian Tang
- Shen Zhou
- Da‑Hua Wu
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Affiliations: Department of Neurology, The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, Hunan 410006, P.R. China, Department of Neurology, Brain Hospital of Hunan, Changsha, Hunan 410007, P.R. China, Marine Biomedical Research Institute of Qingdao Marine Microbiological Engineering & Research Center, Qingdao, Shandong 266071, P.R. China, Department of Rehabilitation Medicine, The People's Hospital of Zhangjiajie, Zhangjiajie, Hunan 427000, P.R. China, State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, P.R. China, College of Pharmacy, Guiyang College of Traditional Chinese Medicine, Guiyang, Guizhou 550002, P.R. China, Service Center of Beijing Tongzhou International Medical Center, Beijing 101117, P.R. China, Laboratory of Innovative Medical Technology, Tsinghua University, Beijing 100084, P.R. China
Published online on: September 26, 2016 https://doi.org/10.3892/mmr.2016.5784
Pages: 4198-4208
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human glioma is the most common type of primary brain tumor and one of the most invasive and aggressive tumors, which, even with treatments including surgery, radiotherapy and chemotherapy, often relapses and exhibits resistance to conventional treatment methods. Developing novel strategies to control human glioma is, therefore, an important research focus. The present study investigated the mechanism of apoptosis induction in U251 human glioma cells by capsaicin (Cap) and dihydrocapsaicin (DHC), the major pungent ingredients of red chili pepper, using the Cell Counting Kit‑8 assay, transmission electron microscopy analysis, flow cytometry analysis, laser scanning confocal microscope analysis and immunohistochemical staining. Treatment of U251 glioma cells with Cap and DHC resulted in a dose‑ and time‑dependent inhibition of cell viability and induction of apoptosis, whereas few effects were observed on the viability of L929 normal murine fibroblast cells. The apoptosis‑inducing effects of Cap and DHC in U251 cells were associated with the generation of reactive oxygen species, increased Ca2+ concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspase‑9 and ‑3. These effects were further conﬁrmed by observations of the anti‑tumor effects of Cap and DHC in vivo in a U251 cell murine tumor xenograft model. These results demonstrate that Cap and DHC are effective inhibitors of in vitro and in vivo survival of human glioma cells, and provide the rationale for further clinical investigation of Cap and DHC as treatments for human glioma.

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