Saffron Crudes and Compounds Restrict MACC1-Dependent Cell Proliferation and Migration of Colorectal Cancer Cells
Nazli Güllü,
Dennis Kobelt,
Hassan Brim,
Shaman Rahman,
Lena Timm,
Janice Smith,
Akbar Soleimani,
Stefano Di Marco,
Silvia Bisti,
Hassan Ashktorab,
Ulrike Stein
Affiliations
Nazli Güllü
Experimental and Clinical Research Center, Charité—Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany
Dennis Kobelt
Experimental and Clinical Research Center, Charité—Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany
Hassan Brim
College of Medicine & Cancer Center, Howard University 2041 Georgia Av. NW, Washington, DC 20059, USA
Shaman Rahman
Experimental and Clinical Research Center, Charité—Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany
Lena Timm
Experimental and Clinical Research Center, Charité—Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany
Janice Smith
Experimental and Clinical Research Center, Charité—Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany
Akbar Soleimani
College of Medicine & Cancer Center, Howard University 2041 Georgia Av. NW, Washington, DC 20059, USA
Stefano Di Marco
Center for Synaptic Neuroscience and Technology, The Italian Institute of Technology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
Silvia Bisti
NetS3 Laboratory Neuroscience and Brain Technologies (NBT), The Italian Institute of Technology (IIT), Via Morego 30, 16128 Genova, Italy
Hassan Ashktorab
College of Medicine & Cancer Center, Howard University 2041 Georgia Av. NW, Washington, DC 20059, USA
Ulrike Stein
Experimental and Clinical Research Center, Charité—Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany
The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron’s anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.
