Effects of the natural protease inhibitor and hormone therapy, alone and in combination, on uterine leiomyoma cells

Camila Bonazza; Rodrigo Aquino Castro; Sheila Siqueira Andrade; Joana Tomomi Sumikawa; Camila Ramalho Bonturi; Yara Aparecida Lobo; Manoel J.B.C. Girao; Maria Luiza V. Oliva

Volume : VII, Issue : I, January - 2018

Effects of the natural protease inhibitor and hormone therapy, alone and in combination, on uterine leiomyoma cells

Camila Bonazza, Rodrigo Aquino Castro, Sheila Siqueira Andrade, Joana Tomomi Sumikawa, Camila Ramalho Bonturi, Yara Aparecida Lobo, Manoel J. B. C. Girao, Maria Luiza V. Oliva

Abstract :

Uterine leiomyoma is a benign tumor, common in women of reproductive age. It is considered a public health problem because surgery is the most effective treatment followed by treatment of major relapse. The EcTI protease inhibitor extracted from Enterolobium contortisiliquum seeds was tested as a modulator of leiomyoma conditions and its effects on the adhesion pathway targeting FAK/Src and p130cas proteins, cell cycle, and cell death were analyzed. We used primary leiomyomatous cells and their respective adjacent tissues cells in culture, treated with 17β–estradiol (E₂), progesterone (P₄), and EcTI, alone and in combination.

The FAK/Src (MAPK) phosphorylated form was increased in adjacent tissue cells while a significant decrease was observed in leiomyomatous cells, which may explain the loss of focal adhesion. In addition, the increased p130cas protein expression in adjacent cells may suggest a protection from apoptosis induced by Anoikis; unlikely, the decrease of this component resulted from treatments in the leiomyomata’s cells stimulated the process. In the cell death pathway, the treatment of leiomyomatous cells with progesterone and EcTI leads to death; this effect is corroborated by the increased expression of the pro–apoptotic Bax protein and decreased expression of the anti–apoptotic protein BcL–2. EcTI, through recruiting the p130cas protein, activates key aspects of the Anoikis process, established by the relationship between the BAX and BcL–2 cell death proteins.