Curcumin Suppresses Proliferation and Migration and Induces Apoptosis on Human Placental Choriocarcinoma Cells via ERK1/2 and SAPK/JNK MAPK Signaling Pathways

摘要

Curcumin, a natural pigment for yellow color that originates from turmeric, is a diarylheptanoid widely studied for its anti-inflammatory, antiangiogenic, antioxidant, and anticancer effects on cells. In placental diseases, including preeclampsia and preterm birth, curcumin reduces proinflammatory cytokines. Even though curcumin is regarded as a novel chemotherapeutic agent with strong apoptotic effects based on phenolic structure, little is known about its functional effects on choriocarcinoma. Therefore, in the present study, we investigated the chemotherapeutic effects of curcumin on choriocarcinoma cells (JAR and JEG3), which are valuable placental models. The results showed that curcumin decreased viability of choriocarcinoma cells in a dose-dependent manner. In addition, proliferative and migratory characteristics of JAR and JEG3 cells were inhibited by curcumin treatment and curcumin-induced apoptotic effects, which were assessed using TUNEL and annexin V/propidium iodide staining. Moreover, curcumin increased depolarization of the mitochondrial membrane based on JC-1 staining and changed expression of apoptotic proteins. Phosphorylation of mitogen-activated protein kinases (MAPK) responsible for regulation of anticancer effects of curcumin were examined for dose-and time-dependent effects. The ERK1/2 and SAPK/JNK and their downstream molecules including P90RSK and c-Jun, respectively, were activated by curcumin. Moreover, pharmacological inhibitors of ERK1/2 (U0126) and SAPK/JNK (SP600125) suppressed ERK1/2 and SAPK/JNK activation respectively, and blockage of P38 MAPK by its inhibitor (SB203580) had a synergistic effect with curcumin. These results indicate that curcumin acts as a novel chemotherapeutic agent on human placental choriocarcinoma cells via activation of ERK1/2 and SAPK/JNK signal transduction cascades.