Garcinol Inhibits the Proliferation of Endometriosis Cells by Regulating Cell Cycle Related Genes and Signaling Pathways

Endometriosis is a common gynecological disease with high recurrence rates after surgery and the lesions keep unlimited proliferative capacity. The effect of garcinol on cell proliferation has not been investigated in endometriosis. Herein, we studied the effect of garcinol on endometriosis by using the immortalized human endometriotic epithelial cell line 12Z and stromal cell line iheESCs. RTCA and EdU assays were used to assess cell proliferation. RNA-Seq was used to discover the differential expression gene (DEG) profile and GSEA, KEGG, protein-protein interaction network and the transcription factor interaction network were analyzed. We found that garcinol inhibited the cell proliferation and S phase DNA synthesis of 12Z and iheESCs cells. There were 548 DEGs in the transcription profiles of the two cell lines. The GSEA results showed that garcinol could inhibit the DNA replication and cell cycle pathways. Among the cell cycle related genes, p21 was increased, while cyclin B1, cyclin E1, CDK2, CDK4, Myc, p27 and E2F1 were significantly decreased after garcinol treatment. The level of cell cycle M phase marker, pH3 Ser10, was also reduced by garcinol. Garcinol could regulate the Akt/c-Jun/ERK1/2 signaling pathways. Garcinol could regulate the protein-protein interaction network and the transcription factor interaction network, in which garcinol increased the transcription factor ATF3 and FOSB expression. In conclusion, garcinol could inhibit the proliferation of endometriosis cells in vitro.