Proliferation of estrogen-responsive mouse tumor cell line B-1F stimulated by Saiboku-to, but inhibited by Scutellaria baicalensis, a component of Saiboku-to.

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.

Methylcobalamin inhibits fibroblast growth factor-8 stimulated proliferation and induces apoptosis in Shionogi carcinoma cells.

SC-3 cells, an androgen-dependent mouse mammary carcinoma cell line, in response to androgen stimuli, induces the secretion of fibroblast growth factor (FGF-8), which in turn increases the proliferation of these cells. We have shown previously that methylcobalamin (MeCbl) decreases the levels of FGF-8 mRNA in SC-3 cells stimulated by testosterone, inhibiting the proliferation of SC-3 cells and inducing apoptosis. In the present study, we analyzed the effects of MeCbl on SC-3 cell proliferation in response to exogenous addition of FGF-8. Thymidine incorporation showed a significant decrease in SC-3 cells cultured with MeCbl. Immunocytochemistry for single-stranded DNA (ssDNA) and DNA fragmentation analysis demonstrated that MeCbl induced apoptosis in SC-3 cells, even in the presence of FGF-8. These results show that the addition of FGF-8 stimulates the proliferation of SC-3 cells under the androgen-depleted condition and that MeCbl might be able to interfere with FGF-8 action.

Establishment of a progesterone-sensitive cell line from human lung cancer.

For deveplopment and function of the lung, progesterone (Prog) fulfils important roles. In a recent report, immunolocalization of Prog and estrogen receptors in non-small cell lung carcinomas were examined and it was shown that the Prog receptor might be a potent prognostic factor. In the present study, a cell line with the sensitivity to Prog was established from a human lung cancer and the growth mechanism was analyzed. The proliferation of established SN96-42 cells was sensitive to Prog and antiprogesterone RU38486 inhibited their proliferation stimulated by Prog. Exposure of these cells to Prog resulted in a decreased formation of leukotriene (LT). The 5-lipoxygenase inhibitor (5-LOX), AA861, effectively stimulated SN96-42 cell proliferation and 5-LOX-catalyzed product(s), especially LTC4, inhibited SN96-42 cell proliferation caused by Prog. Prog-sensitive enhancement of SN96-42 cell proliferation is at least partly mediated through an inhibition of LT formation and these data suggest that 5-LOX and LTs play important roles in SN96-42 cell proliferation stimulated by Prog.