title: Characterization of the anticancer effects of S115, a novel heteroaromatic thiosemicarbazone compound, in vitro and in vivo.
abstract: OBJECTIVE
  To investigate the anticancer effects of S115, a novel heteroaromatic thiosemicarbazone compound in vitro and in vivo.
  
  
  METHODS
  The anti-proliferative action of S115 was analyzed in 12 human and mouse cancer cell lines using MTT assay. Autograft and xenograft cancer models were made by subcutaneous inoculation of cancer cells into mice or nude mice. The mice were orally treated with S115 (2, 8, 32 mg·kg(-1)·d(-1)) for 7 d, and the tumor size was measured every 3 d. Cell apoptosis and cell cycle distribution were examined using flow cytometry, gene expression profile analyses, Western blots and RT-PCR.
  
  
  RESULTS
  The IC50 values of S115 against 12 human and mouse cancer cell lines ranged from 0.3 to 6.6 μmol/L. The tumor growth inhibition rate caused by oral administration of S115 (32 mg·kg(-1)·d(-1)) were 89.7%, 81.7%, 78.4% and 77.8%, respectively, in mouse model of B16 melanoma, mouse model of Colon26 colon cancer, nude mouse model of A549 lung cancer and nude mouse model of SK-OV-3 ovarian cancer. Furthermore, oral administration of S115 (7.5 mg·kg(-1)·d(-1)) synergistically enhanced the anticancer effects of cyclophosphamide, cisplatin, or 5-fluorouracil in mouse model of S180 sarcoma. Treatment of A549 human lung cancer cells with S115 (1.5 μmol/L) induced G0/G1 cell cycle arrest, and increased apoptosis. Furthermore, S115 downregulated the level of ubiquitin, and upregulated the level of Tob2 in A549 cells.
  
  
  CONCLUSIONS
  S115 exerts anticancer effects against a variety of cancer cells in vitro and in grafted cancer models by inducing apoptosis, downregulating ubiquitin and upregulating Tob2.
authors.affiliation: 1] School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China [2] Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Min-yu
authors.initials: MY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Shanghai Kairun Bio Pharm Company, Ltd, Shanghai 201108, China.
authors.forename: Yu-qiong
authors.initials: YQ
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Wei-xia
authors.initials: WX
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Yu-long
authors.initials: YL
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Quan-hai
authors.initials: QH
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013882:Thiosemicarbazones / Q000494:pharmacology*; D059467:Transcriptome / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D013882:Thiosemicarbazones