Antiproliferative effect of Scutellaria barbata D. Don. on cultured human uterine leiomyoma cells by down-regulation of the expression of Bcl-2 protein.
Scutellaria barbata D. Don (Lamiaceae; SB) inhibited the growth of leiomyomal cells (LM). A time-dependent antiproliferative effect was noted when 10(-5) m buserelin, gonadotrophin-releasing hormone (GnRH) agonist or 20-40 microg/mL SB was added. The inhibition of cell growth decreased with the addition of the PKC activator (12-O-tetradecanoylphorbor-13-acetate; TPA) much as it did with the addition of SB, and the decreases in the viable cells caused by the addition of SB were reversed completely by pretreatment with a protein kinase C (PKC) inhibitor (calphostin C). The findings suggest that SB inhibits cell proliferation in cultured human uterine leiomyoma cells accompanied by PKC activation. Next, the study investigated the effect of SB on fetal development for toxicity. Pregnant Sprague-Dawley rats, from gestation day 6-15, were administered 20 g/L or 50 g/L SB in the drinking water and then killed on day 20. No maternal toxicity was observed, however, embryonic loss in the treatment groups was double that of the controls (p < 0.05). No gross morphologic malformations were seen in the treated fetuses. Fetuses exposed to SB were found to be significantly heavier than the controls, an effect that was greater in female fetuses and was not correlated with increased placental size. The results suggest that the SB had no toxicity and that in utero exposure to SB resulted in increased early embryo loss with increased growth in surviving fetuses. On the other hand, Western blot analyses revealed that Bcl-2 protein of a 26 kDa was abundant in leiomyomal cells, but not in normal myometrial cells. The addition of progesterone (100 ng/mL) resulted in a striking increase in Bcl-2 protein expression in the cultured leiomyoma cells. However, the addition of SB (20 microg/mL) resulted in a significant reduction in Bcl-2 protein expression in the cells. The results indicated that human uterine leiomyomal cells express Bcl-2 protein and progesterone enhances its expression, however, SB reduces the expression of Bcl-2 protein in human uterine leiomyoma cells.
Kim
Kyung-Woon
KW
Department of Biological Sciences, Sungkyunkwan University, Chunchun-Dong 300, Suwon, Kyunggi-Do 440-746, Korea.
Jin
Un-Ho
UH
Kim
Dong-Il
DI
Lee
Tae-Kyun
TK
Kim
Min-Sung
MS
Oh
Min-Ju
MJ
Kim
Myung-Sunny
MS
Kwon
Dae Young
DY
Lee
Young-Choon
YC
Kim
Cheorl-Ho
CH
D000818:Animals; D015153:Blotting, Western; D002064:Buserelin / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031363:Scutellaria / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D010703:Phorbol Esters; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D011966:Receptors, LHRH; D011374:Progesterone; D011493:Protein Kinase C; D002064:Buserelin