Elham Nikkhah - Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Irann
Fatemeh Kalalinia - Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Mitra Asgharian Rezaee - Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
Zahra Tayarani-Najaran - Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stromal cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) development and metastasis is controversial. Strong evidence demonstrated that conditioned medium (CM) obtained from MSCs regulates main cellular functions such as proliferation, differentiation, migration, and communication due to its cell secretomes. This study was designed to determine the inhibitory effect of dental pulp stem cells (DPSC) and its extracted conditioned medium (DPSC-CM) in CRC progression.Materials and Methods: The inhibitory effects of DPSC-CM on growth, apoptosis, and migration of CRC cells were evaluated by resazurin, flow cytometry of propidium iodide (PI) stained cells, and wound closure assay, respectively. Western blotting detected the expression of MAPKinase and apoptotic proteins. Also, the homing ability of DPSCs and the invasion ability of CRC cells under indirect co-culture were assayed by the Boyden chamber assay.            Results: DPSC-CM reduced the viability and induced the apoptosis of CRC cells significantly. Western blot analysis confirmed the increase in cytochrome C, phospho-JNK/SAPK to JNK/SAPK ratio, cleaved-caspase ۸ and ۳ in treated CRC cells with DPSC-CM, and decrease in phospho-ERK (P۴۴/۴۲ MAPK) to ERK (P۴۴/۴۲ MAPK) ratio, which are involved in induction of apoptosis and growth inhibition of cancer cells with minimal change in normal cells. Also, DPSCs could migrate (homing ability) to Caco۲ and SW۴۸ cells significantly.Conclusion: To sum up, DPSC-CM had significant apoptotic and growth inhibitory effects on the CRC cells through the MAPKinase and apoptosis signaling pathways.

Apoptosis, Colonic neoplasms, Conditioned medium, Dental pulp, MAP kinase cascade, Stem cells