Low concentrations of trichosanthin induce apoptosis and cell cycle arrest via c‑Jun N‑terminal protein kinase/mitogen‑activated protein kinase activation

Zhang,Duo; Chen,Bin; Zhou,Jian; Zhou,Lin; Li,Qing; Liu,Fei; Chou,Kuang‑Yen; Tao,Lei; Lu,Li‑Ming

doi:10.3892/mmr.2014.2760

Low concentrations of trichosanthin induce apoptosis and cell cycle arrest via c‑Jun N‑terminal protein kinase/mitogen‑activated protein kinase activation

Authors:
- Duo Zhang
- Bin Chen
- Jian Zhou
- Lin Zhou
- Qing Li
- Fei Liu
- Kuang‑Yen Chou
- Lei Tao
- Li‑Ming Lu
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Affiliations: Department of Otolaryngology‑Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University School of Medicine, Shanghai 200031, P.R. China, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Published online on: October 23, 2014 https://doi.org/10.3892/mmr.2014.2760
Pages: 349-356

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Abstract

Trichosanthin (TCS) is a type I ribosome‑inactivating protein, which inhibits cell viability in human epithelial type 2 (HEp‑2) and AMC‑HN‑8 human laryngeal epidermoid carcinoma cells. Although TCS is a potential chemotherapeutic agent, its mechanism of action remains to be elucidated. In the present study, HEp‑2 and AMC‑HN‑8 cells were treated with different concentrations of TCS combined with or without cisplatin. After 5 days of successive treatment, different experimental groups were detected using a cell counting kit‑8 and the collected supernatants were analyzed using a lactate dehydrogenase kit. Flow cytometric assays were performed to detect apoptosis and cell cycle arrest in the HEp‑2 and AMC‑HN‑8 cells, reverse transcription quantitative polymerase chain reaction was performed to detect the levels of p27, p21WAF and western blot analysis was performed to detect changes in c‑Jun N‑terminal protein kinase (JNK)/phosphorylated (phospho)‑JNK, p38/phospho‑p38, extracellular signal‑regulated kinase (ERK)/phospho‑ERK, caspase‑3 and caspase‑9 in the HEp‑2 and AMC‑HN‑8 cancer cells. TCS significantly inhibited the cell viability of the HEp‑2 and AMC‑HN‑8 cells, independently of necrosis. TCS induced apoptosis and increased the percentage of HEp‑2 and AMC‑HN‑8 cells in the S‑phase of the cell cycle. In addition, the JNK/mitogen‑activated protein kinase (MAPK) pathway was activated by TCS in the HEp‑2 and AMC‑HN‑8 cells. Low concentrations of TCS also induced apoptosis and S‑phase cell cycle arrest in the HEp‑2 and AMC‑HN‑8 cells. The antitumor effects of TCS may be associated with JNK/MAPK activation

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