title: Trichosanthin-induced autophagy in gastric cancer cell MKN-45 is dependent on reactive oxygen species (ROS) and NF-κB/p53 pathway.
abstract: Trichosanthin (TCS), isolated from the root tuber of Trichosanthes kirilowii tubers in the Cucurbitaceae family, owns a great deal of biological and pharmacological activities including anti-virus and anti-tumor. TCS has been reported to induce cell apoptosis of a diversity of cancers, including cervical cancer, choriocarcinoma, and gastric cancer, etc. However, whether TCS would induce autophagy in gastric cancer cells was seldom investigated. In current study, human gastric cancer MKN-45 cell growth was significantly inhibited by TCS. The anti-proliferation effect of TCS was due to an increased autophagy, which was confirmed by monodansylcadervarine (MDC) staining, up-regulation of Autophagy protein 5 (Atg5), and conversion of LC3 I to LC3 II (autophagosome marker). In addition, TCS induced reactive oxygen species (ROS) in MKN-45 cells and ROS scavenger N-acetylcysteine (NAC) significantly reversed TCS-induced autophagy. Furthermore, NF-κB/p53 pathway was activated during the process of autophagy induced by TCS and the ROS generation was mediated by it in MKN-45 cells. In vivo results showed that TCS exerted significantly anti-tumor effect on MKN-45 bearing mice. Considering the clinical usage of TCS on other human diseases, these research progresses provided a new insight into cancer research and new therapeutic avenues for patients with gastric cancer.
authors.affiliation: People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, Guangxi, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.affiliation: People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, Guangxi, China.
authors.forename: Qiaoying
authors.initials: Q
authors.lastname: Huang
authors.affiliation: People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, Guangxi, China.
authors.forename: Shunrong
authors.initials: S
authors.lastname: Huang
authors.affiliation: People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, Guangxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Mai
authors.affiliation: People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, Guangxi, China. Electronic address: xiaogaong_zhong88@126.com.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015978:Trichosanthin / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D015978:Trichosanthin; D053148:Caspase 3
keywords: Apoptosis; Autophagy; Gastric cancer; Reactive oxygen species; Trichosanthin