Abstract. We have demonstrated that the proliferation of estrogen-responsive mouse Leydig tumor cell line B-1F is induced via suppression of 5-lipoxygenase activity followed by decrease of leukotrienes (LTs). Additionally, it has been reported that LTD4 induces apoptosis in B-1F cells. In this study, we examined effects of Saiboku-to, a traditional Chinese medicine having suppressive activities for LT production and release, on the proliferation. Saiboku-to promoted, but Scutellaria baicalensis, one of components (herbs) of Saiboku-to, significantly inhibited the proliferation of B-1F cells in vitro and in vivo. The action of Scutellaria baicalensis in B-1F cells was studied in more detail. Although Scutellaria baicalensis consists of flavonoids, iridoids, volatile oils and others, it and its major constituents had no direct effect on estrogen binding sites in B-1F cells. B-1F cells treated with Scutellaria baicalensis showed morphological changes such as nuclear aggregation and fragmentation. DNA fragmentation was also observed, indicating that Scutellaria baicalensis induces apoptosis in B-1F cells and that it or its constituents might be a good resource for searching new drugs, especially anti-cancer drugs. Moreover, Saiboku-to promoted B-1F cell proliferation, but Scutellaria baicalensis inhibited it, showing complexity of action of traditional Chinese medicines.

Abstract.We have studied the effects of saiboku-to, a traditional chinese medicine having suppressive activities for leukotriene production and release, on the proliferation of the estrogen-responsive mouse leydig tumor cell line B-1F. In our previous reports, it is shown that saiboku-to promotes, but Scutellaria baicalensis, one of the components (herbs) of Saiboku-to, significantly inhibits the proliferation of B-1F cells in vitro and in vivo, and induces DnA fragmentation and morphological changes such as nuclear aggregation and fragmentation. In this study, we examined telomerase activity, cell cycle, polyunsaturated fatty acid metabolism and expression of nuclear factor κB (nF-κB) in order to determine the mechanism of growth inhibition in B-1F cells treated with Scutellaria baicalensis. telomerase activity was decreased in a dose-dependent manner in treated B-1F cells. cellular populations in the sub-g0/g1 and g2/M phases were increased, but those in M phase had no change. Although cyclin D1 mrnA was highly expressed in the presence of estradiol (e2), cyclin A and E mRNA levels did not significantly change. When B-1F cells were treated with Scutellaria baicalensis, expression of cyclin D1 was suppressed and that of p21 was inversely increased. Moreover, Scutellaria baicalensis influenced arachidonic and linoleic acid metabolism, and increased production of 13(s)-HoDe. In the presence of e2 Scutellaria baicalensis decreased expression of nF-κB p65 to 0.71-fold in B-1F cells. these results show that Scutellaria baicalensis might induce cell cycle arrest at g1 phase and apoptosis via inhibition of telomerase activity, changes of enzymatic activities in polyunsaturated fatty acid metabolism and suppression of nF-κB.