Inhibitory effects and mechanisms of Siegesbeckia orientalis extract and its bioactive ingredients on proliferation and metastasis of endometrial cancer cells

• Main Authors: Chi-Chang Chang, 張基昌
• Other Authors: Jer-Yiing Houng
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/10946012710355309362

博士 === 義守大學 === 化學工程學系暨生物技術與化學工程研究所 === 103 === Endometrial cancer is one of the most common uterine cancers in the United States and Europe. In Taiwan, the incidence of endometrial cancer is second only to cervical cancer and its cases are increasing gradually. Treatment for endometrial cancer usually includes surgery and the postoperative combination therapy with radiation, chemotherapy and hormonal treatment for advanced endometrial cancer. However, the efficiency of these therapeutic strategies remains limited. Therefore, developing an efficacious adjuvant drug for endometrial cancer might be most pressing matter of the moment. Siegesbeckia orientalis linne is an herbaceous and dicotyledonous plant, which belongs to Asteraceae. It is a traditional Chinese medicinal herb endowing with the medicinal facts to treat limb paralysis, rheumatism, joint pain, aching pain, lassitude, weakness, hypertension, detumescence, detoxification, trauma, bleeding. However, these bioactivities have not yet been well examined scientifically. In this study, we investigated whether S. orientailis crude extract (SOE) and its potential active agents induce endometrial cancer cell apoptosis and whether they can inhibit metastasis of endometrial cancer cells. The results revealed that SOE had a significant cytotoxic effect on endometrial carcinoma RL95-2 cells and arrested cells in the G2/M phase of cell cycle. From the result of GC-MS analysis, caryophyllene oxide (CPO) was the major bioactive ingredients of SOE. Transforming growth factor β (TGFβ) is a multifunctional cytokine involved in tumorigenesis in human cancer including proliferation, cell survival, angiogenesis, migration and invasion during tumor progression. This study shows that SOE and CPO can inhibit TGFβ1-induced cell wound healing, cell invasion and cell migration in a dose-dependent manner in two endometrial cancer cell lines, RL95-2 and HEC-1A cells. The TGFβ1-induced epithelial-mesenchymal transition, including the loss of cell-cell junction and the lamellipodia-like structures, could be reversed by SOE and CPO. Moreover, SOE and CPO inhibited significantly the expression of MAPK pathway, p-Akt, MMP-9 and MMP-2 in RL95-2 cells dose-dependently. The inhibition of activation of pro-MMPs to MMPs by suppressing the uPA activity may be involved in the possible molecular mechanism.