Article Publish Status: FREE
Abstract Title:

Luteolin Inhibits Proliferation and Induces Apoptosis of Human Placental Choriocarcinoma Cells by Blocking the PI3K/AKT Pathway and Regulating Sterol Regulatory Element Binding Protein Activity.

Abstract Source:

Biol Reprod. 2016 Aug 31. Epub 2016 Aug 31. PMID: 27580988

Abstract Author(s):

Whasun Lim, Changwon Yang, Fuller W Bazer, Gwonhwa Song

Article Affiliation:

Whasun Lim

Abstract:

Luteolin is a natural compound known for its anti-cancer effects on various human cancers by regulating signal transduction cascades. However, the effects of luteolin on human placental choriocarcinoma are not known. Results of the present study revealed that luteolin decreased viability of JAR and JEG-3 cells, which are valuable placental models, in a dose-dependent manner and it induced apoptosis and loss of mitochondrial membrane potential in JAR and JEG-3 cells. The results also suggested that the PI3K/AKT pathway was inhibited by luteolin treatment of JAR and JEG-3 cells in a dose- and time-dependent manner. Next, we established effects of luteolin in the presence of pharmacological inhibitors of PI3K/AKT, ERK1/2 MAPK and mTOR on proliferation of JAR and JEG-3 cells. In addition, these inhibitors were used to verify phosphorylation of AKT, GSK3β and ERK1/2 and confirm mechanisms regulated by luteolin in JAR and JEG-3 cells. We also determined SREBP1 and SREBP2 expression to investigate regulatory function of luteolin in lipid metabolism in JAR and JEG-3 cells. Expression of both SREBP1 and SREBP2 mRNAs was significantly reduced, but onlySREBP1 protein was influenced by luteolin. We compared viability of JAR and JEG-3 cells in response to luteolin alone or in combination with other chemotherapeutic drugs (etoposide, cisplatin and paclitaxel) and found that luteolin has synergistic effects with the conventional chemotherapeutic drugs as an anti-cancer agent. Collectively, these results showed that luteolin plays an important role in the treatment of human choriocarcinoma cells by inhibiting the PI3K/AKT/mTOR/SREBP cascade and expression of lipogenic genes.

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