Cyclin D1–CDK4 inhibitors, such as arcyriaflavin A, may be promising candidates for the treatment of endometriosis, according to a new study. However, more research is warranted to provide additional information on the efficacy of these compounds.
The study, “Arcyriaflavin a, a cyclin D1–cyclin-dependent kinase4 inhibitor, induces apoptosis and inhibits proliferation of human endometriotic stromal cells: a potential therapeutic agent in endometriosis,” was published in the journal Reproductive Biology and Endocrinology.
Cyclin D1 is a protein that interacts with the enzymes CDK 4/6 to regulate cell division, one mechanism that is faulty in endometriosis. Previous research has suggested that inhibition of cyclin D1 with a molecule known as miR-503 may have potential therapeutic effects in this disease, but only a few studies have addressed this matter.
Now, researchers using cultures of endometriotic cyst stromal cells (ECSCs) obtained from the ovarian endometriotic tissues of 32 women, investigated the effects of arcyriaflavin A, a cyclin D1–CDK4 inhibitor, on several parameters, such as cell proliferation and death.
“We hypothesized that cyclin D1 and CDK inhibitors might alleviate endometriosis,” the researchers wrote. “Arcyriaflavin A, a representative cyclin D1–CDK4 inhibitor, exhibited potent inhibition of cyclin D1–CDK4. Furthermore, it was previously described as a novel antiviral compound and was reported to induce cancer cells apoptosis. Therefore, we designed the present study to evaluate the efficacy of arcyriaflavin A in treating endometriosis.”
Results showed that arcyriaflavin A significantly inhibited cell survival and proliferation, as well as the development of new blood vessels in ECSCs, which contribute to the progression of endometriosis.
“We demonstrated that the cyclin D1-CDK4 inhibitor, arcyriaflavin A, exerted therapeutic effects on ECSCs that are similar to those of miR-503, which is considered a promising candidate for the treatment of endometriosis,” researchers wrote. “Future studies on the effects of cyclin D1-CDK4 inhibitors on endometriosis may provide useful information on the pathogenesis of this condition.”
But there are some limitations in this study. “First, the effects of arcyriaflavin A were evaluated only in ECSCs, but not in normal endometrial stromal cells,” researchers wrote. “Another limitation is the study design. There is currently no established protocol for assessing the effects of arcyriaflavin A on endometriotic lesions in vivo.”