1.Progress in study of the structure, catalytic mechanism and inhibitors of aromatase.
Jing FU ; Zhonghua SHEN ; Feixiong CHENG ; Guixia LIU ; Weihua LI ; Yun TANG
Acta Pharmaceutica Sinica 2012;47(1):18-28
Aromatase is a key enzyme responsible for in vivo estrogen biosynthesis. Inhibition of the activity of the aromatase has become an alterative way for treatment of breast cancer. In this review, the structure and catalytic mechanism of the aromatase is briefly introduced followed by thorough review of the progress in the study of the steroidal and non-steroidal aromatase inhibitors. This review is focused on the natural compounds that exhibit the aromatase inhibition, which include flavonoids, xanthones, coumarins, and sesquiterpenes. The structure-activity relationship of these compounds is also discussed.
2.Blocking lhh Signaling Pathway Inhibits the Proliferation and Pro-motes the Apoptosis of PSCs
XU KAI ; GUO FENGJING ; ZHANG SHUWEI ; LIU CHENG ; WANG FEIXIONG ; ZHOU ZHIGUO ; CHEN ANMIN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(1):39-44
The roles of Indian hedgehog (Ihh) signaling pathway in the proliferation and apoptosis of precartilaginous stem cells (PSCs) were investigated.PSCs,labeled with fibroblast growth factor receptor 3 (FGFR-3),were isolated from neonatal rats by immanomagnetic separation.After identifi-cation with FGFR-3 and Col Ⅱ,the cells were incubated with different concentrations of cyclopamine (cyclo),the specific inhibitor of lhh signaling pathway.The morphologic changes of the cells were observed under the inverted phase contrast microscope.The mRNA expression levels of Ibh,para-thyroid hormonerelated peptide (PTHrP),protein Patched (Ptch),Bcl-2 and p21 were detected by RT-PCR.The protein expression levels of Ihh and Ptch were measured by Western blot.MTT assay was used to examine the effects of cyclo on proliferation of PSCs.Apoptosis rate of PSCs was exam-ined by Annexin V/PI assay of flow cytometric analyses.After PSCs were incubated with cyclo,ob-vious morphologic changes were observed as compared with the control group.The mRNA expres-sion levels of PTHrP,Ptch and Bcl-2 were decreased to varying degrees in a cyclo dose-dependent manner.However,the expression levels of lhh and p21 mRNA were increased.The protein expres-sion of Ptch and Ihh had the same change as the mRNA expression.Meanwhile,cyclo could obvi-ously inhibit the proliferation and promote the apoptosis of PSCs.The results indicated that Ihh sig-naling pathway plays an important role in regulating the proliferation and apoptosis of PSCs,which is probably mediated by Bcl-2 and p21.