Robin Fröbom1, Felix Sellberg2, Cheng Xu3, Allan Zhao3, Catharina Larsson4,5, Wenn-Onn Lui4,5, Inga-Lena Nilsson6, Erik Berglund7, Robert Bränström6. 1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden robin.frobom@ki.se. 2. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 3. The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 4. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 5. Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden. 6. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 7. Division of Transplantation Surgery, CLINTEC, Karolinska Institute, and Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden.
Abstract
BACKGROUND/AIM: DOG1 is a calcium-activated chloride channel that has gained attention as a promising drug target due to its involvement in several processes essential for tumor development and progression. DOG1 is overexpressed in >95% of gastrointestinal stromal tumors (GIST). The aim was to determine DOG1 inhibition antitumoral effects on GIST. MATERIALS AND METHODS: Human GIST (GIST-T1 and GIST882) cell lines were used to study the effect of DOG1 inhibitors on chloride currents, viability, colony formation, and cell cycle. RESULTS: CaCCinh-A01 decreased chloride currents. CaCCinh-A01 and T16inh-A01 reduced GIST cell viability and CaCCinh-A01 affected cell cycle distribution leading to G1 cell-cycle arrest. CaCCinh-A01 also increased the sub-G1 phase population, indicative of apoptosis, in GIST882. CaCCinh-A01 strongly reduced the colony forming ability of the cells, whereas T16inh-A01 did not. CONCLUSION: DOG1 inhibition has antitumoral effects in GIST cells in vitro, and could potentially serve as a target for GIST therapy. Copyright
BACKGROUND/AIM: DOG1 is a calcium-activated chloride channel that has gained attention as a promising drug target due to its involvement in several processes essential for tumor development and progression. DOG1 is overexpressed in >95% of gastrointestinal stromal tumors (GIST). The aim was to determine DOG1 inhibition antitumoral effects on GIST. MATERIALS AND METHODS:Human GIST (GIST-T1 and GIST882) cell lines were used to study the effect of DOG1 inhibitors on chloride currents, viability, colony formation, and cell cycle. RESULTS:CaCCinh-A01 decreased chloride currents. CaCCinh-A01 and T16inh-A01 reduced GIST cell viability and CaCCinh-A01 affected cell cycle distribution leading to G1 cell-cycle arrest. CaCCinh-A01 also increased the sub-G1 phase population, indicative of apoptosis, in GIST882. CaCCinh-A01 strongly reduced the colony forming ability of the cells, whereas T16inh-A01 did not. CONCLUSION:DOG1 inhibition has antitumoral effects in GIST cells in vitro, and could potentially serve as a target for GIST therapy. Copyright
Authors: Kristina Jansen; Martina Kluth; Niclas C Blessin; Claudia Hube-Magg; Michael Neipp; Hamid Mofid; Hannes Lárusson; Thies Daniels; Christoph Isbert; Stephan Coerper; Daniel Ditterich; Holger Rupprecht; Albert Goetz; Christian Bernreuther; Guido Sauter; Ria Uhlig; Waldemar Wilczak; Ronald Simon; Stefan Steurer; Eike Burandt; Daniel Perez; Jakob R Izbicki; Frank Jacobsen; Till S Clauditz; Andreas H Marx; Till Krech Journal: Histol Histopathol Date: 2022-06-01 Impact factor: 2.130
Authors: Kristina Jansen; Franziska Büscheck; Katharina Moeller; Martina Kluth; Claudia Hube-Magg; Niclas Christian Blessin; Daniel Perez; Jakob Izbicki; Michael Neipp; Hamid Mofid; Thies Daniels; Ulf Nahrstedt; Christoph Fraune; Frank Jacobsen; Christian Bernreuther; Patrick Lebok; Guido Sauter; Ria Uhlig; Waldemar Wilczak; Ronald Simon; Stefan Steurer; Eike Burandt; Andreas Marx; Till Krech; Till Clauditz Journal: PeerJ Date: 2021-08-03 Impact factor: 2.984