Abstract. in the present study, the potential of curcumin to stimulate proliferation, stemness acting signals and migration of 3t3-l1 preadipocytes and the associated molecular mechanisms were investigated. low concentrations of curcumin stimulated cell proliferation, whereas high concentrations were cytotoxic to 3t3-l1 cells. in particular, application of 0.02 µM of curcumin for 24 h resulted in significantly increased cell proliferation and was determined to be the optimal treatment for this study. in a colony-forming cell assay, cells treated with 0.02 µm of curcumin showed an approximately 1.5-fold increase in colony formation. curcumin treatment up-regulated the proliferation-related marker proteins coupled with increased cell growth, telomerase activity and overexpression of stemness acting signals, which was associated with activation of the phosphoinositide 3-kinase (Pi3K) pathway. In addition, curcumin significantly inactivated p38 mitogen-activated protein kinases (maPK) and stressactivated protein kinase/c-jun n-terminal kinases (SarK/ jnK), coupled with inhibition of p53 and p21 tumor suppressor gene products. In addition, curcumin significantly increased cell migration through activation of migration-associated transcription factors. therefore, these results clearly show that activation of cell proliferation by curcumin is associated with improved stem cell potency in 3t3-l1 preadipocytes.Introduction curcumin (diferuloylmethane) is a natural polyphenol derived from the plant Curcuma longa, which is used in some cultures for the treatment of diseases associated with oxidative stress and inflammation (1). Due to its ability to scavenge free radicals and inhibit inflammation, curcumin has been investigated for cancer chemoprevention and tumor growth suppression (2-6). Previous results have indicated that this compound has been recognized as a promising anticancer drug due to its efficient induction of proliferation arrest and cell death, including apoptosis and necrosis, through diminishing reactive oxygen species (roS) generation in a variety of tumor cells (7-12). furthermore, curcumin has also been reported to prevent tumor-induced t cell apoptosis (13). also, overwhelming in vitro evidence and completed clinical trials suggest that curcumin may prove useful for chemoprevention of human colon cancer (14). Some reports have also suggested the possibility that curcumin can reduce oxidative damage and cognitive deficits associated with aging (15-17). In addition, studies of animal models have suggested that curcumin may be beneficial in neurodegenerative conditions, such as alzheimer's disease (ad) (18-20) and focal cerebral ischemia (21). furthermore, curcumin treatment can protect hippocampal neurons against excitotoxic and traumatic injury (22,23). therefore, curcumin has attracted commercial interest as a useful medicinal reagent. a stem cell is a special type of cell with a unique capacity to renew itself, to give rise to specialized cell types, and to migrate, proliferate and survive (24). altho...