title: 1‑calcium phosphate‑uracil, a synthesized pyrimidine derivative agent, has anti‑proliferative, pro‑apoptotic and anti‑invasion effects on multiple tumor cell lines.
abstract: 1‑calcium phosphate‑uracil (1‑CP‑U), a synthetic pyrimidine derivative, has been documented to demonstrate a variety of different biological activities. However, the potency and mechanisms of this agent's anti-cancer activity have not been elucidated to date. In the present study, the anti‑cancer effects of 1‑CP‑U were examined in a range of in vitro assays. Different cell lines were treated with 1‑CP‑U at varied concentrations (0.7, 1.0, 1.4 µmol/l) for indicated durations. The cell proliferation was then examined by MTT assay. The cellular apoptotic effects were detected by Hoechst 33342 and Annexin V/propidium iodide staining, while the capacity of 1‑CP‑U on invasion and migration were examined by cell invasion and wound healing assays. The expression of matrix metalloproteinase proteins, as well as pro‑ and antiapoptotic proteins was detected by western blotting analysis. The results identified that 1‑CP‑U was able to inhibit the viability of SKOV3, HeLa, SMMC‑7721 and A549 cell lines in a dose‑ and time‑dependent manner, while it exerted only marginal toxic effects on non‑cancerous cells. The IC50 concentration of 1‑CP‑U for tumor cell lines was ~1.0 µmol/l. The growth inhibition induced by 1‑CP‑U was accompanied by a broad spectrum of pro‑apoptotic activities, in which different cell lines varied in their sensitivity to 1‑CP‑U. Meanwhile, the increased expression of the pro‑apoptotic protein B-cell lymphoma-2 (Bcl-2)-associated X and a marked reduction of Bcl‑2 levels were associated with increased 1‑CP‑U concentrations. Additionally, anti‑migration and anti‑invasion effects of 1‑CP‑U were evidently associated with the downregulation of matrix metalloproteinase proteins. Of note, it was observed that 1‑CP‑U signiﬁcantly inhibited both the migration and invasion at a lower concentration, as compared with the dose required to achieve signiﬁcant inhibition of apoptosis. These results indicated that 1‑CP‑U appeared to be a more effective inhibitor of cell migration and invasion, rather than of apoptosis. In conclusion, the present study was the first, to the best of our knowledge, to demonstrate the function of 1‑CP‑U in tumor proliferation, apoptosis and invasion with specific effects against cancer cells in vitro, suggesting 1‑CP‑U as a potential novel anticancer agent.
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xinlian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hongqian
authors.initials: H
authors.lastname: Liu
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Laboratory of Cell and Gene Therapy, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Shanling
authors.initials: S
authors.lastname: Liu
authors.affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C000598413:1-calcium phosphate-uracil; D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D014498:Uracil; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2