title: Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+‑mediated mitochondrial pathway.
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.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, Hunan 410006, P.R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Neurology, Brain Hospital of Hunan, Changsha, Hunan 410007, P.R. China.
authors.forename: Guang-Hong
authors.initials: GH
authors.lastname: Xiang
authors.affiliation: Marine Biomedical Research Institute of Qingdao Marine Microbiological Engineering & Research Center, Qingdao, Shandong 266071, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of Rehabilitation Medicine, The People's Hospital of Zhangjiajie, Zhangjiajie, Hunan 427000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, P.R. China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Guiyang College of Traditional Chinese Medicine, Guiyang, Guizhou 550002, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Service Center of Beijing Tongzhou International Medical Center, Beijing 101117, P.R. China.
authors.forename: You-Ren
authors.initials: YR
authors.lastname: Zhang
authors.affiliation: Laboratory of Innovative Medical Technology, Tsinghua University, Beijing 100084, P.R. China.
authors.forename: Jin-Tian
authors.initials: JT
authors.lastname: Tang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, Hunan 410006, P.R. China.
authors.forename: Shen
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, Hunan 410006, P.R. China.
authors.forename: Da-Hua
authors.initials: DH
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D002212:Capsicum / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D017382:Reactive Oxygen Species; D002211:Capsaicin; C012906:dihydrocapsaicin