Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis

What is it about?

Ten percent of women of reproductive age suffer from symptoms of endometriosis, such as pelvic pain and infertility. Although endometriosis is known as estrogen-dependent inflammatory disease, the detailed molecular mechanism regarding the initiation and progression of endometriosis has not yet been elucidated. To treat endometriosis, systematic estrogen deficiency therapies have conducted. This therapy significantly relieves the symptoms of endometriosis but causes harmful side effects in estrogen target tissues, such as the bone and brain, of the reproductive-aged endometriosis patients. Anti-inflammatory therapy, such as COX-2 inhibitors, is employed to treat endometriosis. However, this therapy also generates side effects in women with endometriosis. To overcome the defects of current endometriosis treatments, we need to define the unique cellular pathway that drives endometriosis to develop new drugs for endometriosis. Our studies have demonstrated that the steroid receptor coactivator (SRC) 1 isoform/estrogen receptor (ER)β axis was a key specific driver for endometriosis progression because this axis prevented TNFα-induced apoptosis and activated inflammasome-mediated inflammatory signaling to stimulate the growth of endometriotic lesions. Bufalin, a small molecular inhibitor against the function of SRCs, significantly targeted this SRC-1 isoform/ERβ axis in endometriotic lesions and then endoplasmic reticulum-induced apoptosis in epithelial cells and pyroptosis in stromal cells of endometriotic lesions. The combination of pyroptosis and apoptosis synergistically kills the endometriotic lesions to effectively suppress endometriosis progression.

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