BACKGROUND: The discovery of cisplatin's antitumor activity led to a great interest in the potential application of coordination compounds as chemotherapeutic agents. It is essential to identify new compounds that selectively inhibit tumor proliferation, evading secondary effects and resistance associated with chemotherapeutics. METHODS: The in vitro antiproliferative potential of an organotin(IV) compound was evaluated using colorectal and hepatocellular carcinoma, mammary gland adenocarcinoma cell lines, and human fibroblasts. Tumor cell death was evaluated by fluorescence microscopy and flow cytometry for the Sn(IV) compound and also for a Co(II) compound bearing 1,10-phenanthroline-5,6-dione as ligand. Comparative proteomic analysis for both compounds was assessed in the colorectal cancer cell line. RESULTS: The Sn(IV) compound presented a high cytotoxic effect in colorectal and hepatocellular carcinoma cell lines (IC50 of 0.238 ± 0.011 μM, 0.199 ± 0.003 μM, respectively), and a lower cytotoxicity in human fibroblasts. Both compounds induced cell apoptosis and promoted the overexpression of oxidative stress-related enzyme superoxide dismutase [Cu-Zn] (SODC). The Co(II) compound induced a decreased expression of anti-apoptotic proteins (translationally-controlled tumor protein and endoplasmin), and the Sn(IV) compound decreased expression of proteins involved in microtubule stabilization, TCTP, and cofilin-1. CONCLUSIONS: Our data reveals a high in vitro antiproliferative potential against cancer cell lines and a moderate selectivity promoted by the Sn(IV) compound. Proteomic analysis of Sn(IV) and Co(II) compounds in the colorectal cancer cell line allowed an insight to their mechanisms of action, particularly by affecting the expression of proteins typically deregulated in cancer, and also suggesting a promising therapeutic potential for both compounds.
BACKGROUND: The discovery of cisplatin's antitumor activity led to a great interest in the potential application of coordination compounds as chemotherapeutic agents. It is essential to identify new compounds that selectively inhibit tumor proliferation, evading secondary effects and resistance associated with chemotherapeutics. METHODS: The in vitro antiproliferative potential of an organotin(IV) compound was evaluated using colorectal and hepatocellular carcinoma, mammary gland adenocarcinoma cell lines, and human fibroblasts. Tumor cell death was evaluated by fluorescence microscopy and flow cytometry for the Sn(IV) compound and also for a Co(II) compound bearing 1,10-phenanthroline-5,6-dione as ligand. Comparative proteomic analysis for both compounds was assessed in the colorectal cancer cell line. RESULTS: The Sn(IV) compound presented a high cytotoxic effect in colorectal and hepatocellular carcinoma cell lines (IC50 of 0.238 ± 0.011 μM, 0.199 ± 0.003 μM, respectively), and a lower cytotoxicity in human fibroblasts. Both compounds induced cell apoptosis and promoted the overexpression of oxidative stress-related enzyme superoxide dismutase [Cu-Zn] (SODC). The Co(II) compound induced a decreased expression of anti-apoptotic proteins (translationally-controlled tumor protein and endoplasmin), and the Sn(IV) compound decreased expression of proteins involved in microtubule stabilization, TCTP, and cofilin-1. CONCLUSIONS: Our data reveals a high in vitro antiproliferative potential against cancer cell lines and a moderate selectivity promoted by the Sn(IV) compound. Proteomic analysis of Sn(IV) and Co(II) compounds in the colorectal cancer cell line allowed an insight to their mechanisms of action, particularly by affecting the expression of proteins typically deregulated in cancer, and also suggesting a promising therapeutic potential for both compounds.
Authors: Pedro Pedrosa; Rita Mendes; Rita Cabral; Luísa M D R S Martins; Pedro V Baptista; Alexandra R Fernandes Journal: Sci Rep Date: 2018-07-30 Impact factor: 4.379
Authors: Ana Soraia Mendo; Sara Figueiredo; Catarina Roma-Rodrigues; Paula A Videira; Zhen Ma; Mário Diniz; Miguel Larguinho; Pedro M Costa; João C Lima; Armando J L Pombeiro; Pedro V Baptista; Alexandra R Fernandes Journal: J Biol Inorg Chem Date: 2015-06-16 Impact factor: 3.358
Authors: Daniel V Luís; Joana Silva; Ana Isabel Tomaz; Rodrigo F M de Almeida; Miguel Larguinho; Pedro V Baptista; Luísa M D R S Martins; Telma F S Silva; Pedro M Borralho; Cecília M P Rodrigues; António S Rodrigues; Armando J L Pombeiro; Alexandra R Fernandes Journal: J Biol Inorg Chem Date: 2014-01-31 Impact factor: 3.358
Authors: M Luísa Corvo; Ana Soraia Mendo; Sara Figueiredo; Rogério Gaspar; Miguel Larguinho; M Fátima C Guedes da Silva; Pedro Viana Baptista; Alexandra R Fernandes Journal: Pharm Res Date: 2016-03-31 Impact factor: 4.200