Differential regulation of protein kinase C activity by modulating factors and Euonymus alatus (Thunb.) Sieb in human myometrial and uterine leiomyomal smooth muscle cells

Abstract

Human myometrial smooth muscle cells (MSMC) showed high protein kinase C (PKC) activity when a maximal dose of PKC-activating phorbol ester was used, while uterine leiomyomal cells (ULMC) showed only 6-12% of PKC activity. MSMC exhibited a low proliferation rate, whereas ULMC exhibited a high proliferation rate. These different cell types of MSMC and ULMC responded to 10 U/mL thrombin, with a twofold stimulation of PKC activity. Downregulation of PKC activity was found when MSMC were treated with phorbol ester or with transforming growth factor-beta2. We concluded that differences in PKC activity exist between MSMC and ULMC, which may be related to their different proliferative activity. ULMC treated with Euonymus alatus (Thunb.) Sieb (EA), known as "gui-jun woo" in Korea, which is used for leiomyomal tumors, exhibited a much lower proliferation rate than untreated cells, suggesting that EA inhibited the cellular proliferation of ULMC. The PKC activity of MSMC by EA treatment (50 microg/mL) changed little. ULMC showed increased PKC activity by addition of EA, indicating that PKC is activated by EA. The EA-treated ULMC were differentiated into phenotypes characteristic for normal untransformed cells, since the EA-treated cells possess higher PKC activity than untreated cells.

Effect of different ingredients in traditional Korean medicine for human uterine leiomyoma on normal myometrial and leiomyomal smooth muscle cell proliferation

“…Similarly, anti-cancer activities of S. barbata, E. alatus, and isoliquiritigenin, the latter a component of S. suberectus, have been determined by induction of cell apoptosis via caspase-3 activation in uterine leiomyomal smooth muscle cells (Lee et al, 2005;Kim et al, 2006Kim et al, , 2008aKim et al, , 2008b. C. zedoaria has also been reported as beneficial in the treatment of uterine cervical neoplasia (Moura et al, 2002).…”

Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model

“…Therefore, various natural product-based studies have been conducted in major therapeutic areas, such as cancer, immune mechanisms, anti-infection, diabetes, and metabolic disorders (2,18). Among these candidates, EA extracts have been extensively studied in vitro and in vivo (7,(19)(20)(21), but the effect of EA treatment on the immune response remains unclear. Therefore, in this study, the immunostimulatory effects of EA were investigated in macrophages, splenocytes, and an immunosuppressed rat model.…”

Evidence-Based Management of Uterine Fibroids With Botanical Drugs-A Review

“…EA also demonstrated the ability to increase PKC activity in uterine leiomyoma cells and a slight increase in the normal myometrial cell. The activity of PKC is lesser in leiomyoma cell as compared to normal myometrium; however, the exact role of PKC in the pathogenesis of UF is not well established as of now ( Lee et al, 2005 ). Even so, it was proposed that PKC could be involved in the downstream pathway of TGF-beta2, which is known to contribute to fibroid development ( Laping et al, 2007 ).…”