苦蘵在台灣及世界其它國家常為草藥被使用，它曾用於治療糖尿病、肝癌、氣喘、及傷寒。再我們先期許實驗中Physalis angulata發現抑制人類乳癌細胞增生及誘導細胞凋亡，再這研發中我們更進一步能發現Physalis angulata能降低Cyclin A 濃度及Cdc2活性，減低Cdc25c而增加細胞週期蛋白抑制劑p21 waf1/cip1及p27 Kip1，並能增加Chk2及Wee1的濃度。 從實驗結果看出P.A能經由三路徑產生細胞週期提止於G2/M期為(1)抑制Cyclin A、Cyclin B的濃度(2)增加細胞週期蛋白抑制激酶p21 waf1/cip1及p27 Kip1濃度(3)可能增加Chk2導致Cdc25c磷酸化，而使Cdc2減低，增加Wee1而使細胞分化週期停滯。 綜合實驗結果顯示，P.A活化Chk2而抑制Cdc25c，也可能活化細胞週期蛋白依賴抑制激酶p21 waf1/cip1及p27 Kip1而導致乳癌細胞分裂停止於G2/M。; Physalis angulata (PA) is employed in herbal medicine in Taiwan and some countries in the world. It was used to treat diabetes, hepatitis, asthma and malaria. In our preliminary study, we found that PA could inhibit the progression of proliferation and induce apoptosis in human breast cancer cells. In this study, we found that PA treatment decrease cyclin A level, decrease Cdc2 activity, increase Cdc2 phosphorylation, decrease Cdc25c and enhance the expression of the cell cycle inhibitor, p21waf1/cip1 and P27Kip level. Furthermore, it increased both the levels of Chk2 and Wee1 kinase. From these results, we conclude that PA arrests MDA-MB 231 cells at G2/M phase through (i) by inhibiting cyclin A level, cyclin B in high concentration of PA, and Cdc2 (ii) by increasing p21waf1/cip1 and P27Kip levels, (iii) by increasing Chk2 causing a increasing Cdc25c phosphorylation/inactivation inducing a decrease in Cdc2 levels and an increase in Wee1 levels. Taken together, these results suggest that the effect of Physalis angulata on the levels of phosphorylated/inactivated Cdc25C are mediated by Chk2 activation, at least in part, via p21waf1/cip1 and P27Kip cyclin- dependent kinase inhibitors pathway to arrest cells at G2/M phase in breast cancer carcinoma .
