Department of Biomaterial Control, Dong-Eui University, Busan 614-714, Republic of Korea.
Int J Mol Med. 2011 Sep;28(3):429-35. doi: 10.3892/ijmm.2011.680. Epub 2011 Apr 20.
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 stress-activated 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.
在本研究中,研究了姜黄素刺激 3T3-L1 前脂肪细胞增殖、干细胞作用信号和迁移的潜力及其相关的分子机制。低浓度的姜黄素刺激细胞增殖,而高浓度的姜黄素对 3T3-L1 细胞则具有细胞毒性。特别是,应用 0.02µM 的姜黄素处理 24 小时导致细胞增殖显著增加,被确定为本研究的最佳处理方法。在集落形成细胞测定中,用 0.02µM 的姜黄素处理的细胞显示集落形成增加约 1.5 倍。姜黄素处理上调了与细胞生长、端粒酶活性和干细胞作用信号的过度表达相关的增殖相关标记蛋白,这与磷酸肌醇 3-激酶 (PI3K) 途径的激活有关。此外,姜黄素还显著失活了 p38 丝裂原激活蛋白激酶 (MAPK) 和应激激活蛋白激酶/c-Jun N-末端激酶 (SARK/JNK),同时抑制了 p53 和 p21 肿瘤抑制基因产物。此外,姜黄素通过激活与迁移相关的转录因子显著增加了细胞迁移。因此,这些结果清楚地表明,姜黄素激活细胞增殖与 3T3-L1 前脂肪细胞中干细胞活力的提高有关。