SULFORAPHANE, AN ORGANIC ISOTHIOCYANATE FOUND IN CRUCIFEROUS VEGETABLES, REGULATES EXPRESSION OF GENES INVOLVED IN HIPPO SIGNALING AND FIBROTIC PHENOTYPE IN UTERINE FIBROID CELLS

Uterine fibroids are fibrotic tumors of uterus associated with abnormal menstrual bleeding and pelvic pain or pressure. Our recent data showed that Hippo signaling was dysregulated (OFF) in uterine influenced by extracellular matrix (ECM) stiffness. When is ‘OFF’, the downstream effectors, YAP/TAZ, interact TEAD to induce transcription genes involved cell growth fibrosis. Sulforaphane (SFN) an organic isothiocyanate abundantly present cruciferous vegetables tumor-preventing properties. We tested hypothesis SFN could alter phenotype fibroid cells. To assess effect on proliferation, (P51F, fib) myometrial (P51M, myo) cells were treated vehicle (DMSO) at increasing concentration (0.5, 1, 5, 10, 20 μM) for 24 hrs MTS assay performed. quantify mRNA levels phenotype, both types μM real-time qPCR performed using gene-specific primers. The student’s t-test used analysis p≤0.05 considered as significant. Fibroid grew differentially response treatment. maximum inhibition viability (44%) observed SFN, compared (14%). Consistently, proliferative gene, CCND1 reduced (p=0.02), but not (p=0.16) SFN. found transcriptional effectors signaling, TEAD1 (p<0.001 fib p<0.004 myo), YAP1, cells, suggesting SFN-mediated inactivation TEAD. increased transcript cytoplasmic component SAV1, treatment (p=0.0002) (p=0.04) further supported alteration signaling. Of note, decreased major ECM components, COL1A1 (p=6.099E-05 p=0.0001 FN1 (p=0.0003 VCAN (p=0.007 p=0.003 Also, we PAI-1, a known mediator fibrosis, (p=0.003), (p=0.02). Furthermore, did affect MMP2 (p=0.38 p=0.58 selectively TIMP1 (p=0.05) (p=0.29). TEAD-specific actions regulated expression Further study warranted explore role this natural compound abundant effects fibroids.