Juan-Cheng Yang1, Yang-Chang Wu1,2,3, Yun-Hao Dai4,5, Guan-Yu Chen5, Chih-Hsin Tang6,7,8, Wei-Chien Huang5,7,9,2. 1. Chinese Medicine Research and Development Center, Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.; yachwu@mail.cmu.edu.tw qq9113054@gmail.com. 2. The Biotechnology Department, College of Medical and Health Science, Asia University, Taichung, Taiwan, R.O.C. 3. Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C. 4. School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. 5. Chinese Medicine Research and Development Center, Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C. 6. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan, R.O.C. 7. Chinese Medicine Research Center, Drug Development Center, China Medical University, Taichung, Taiwan, R.O.C. 8. Department of Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan, R.O.C. 9. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: Estrogen receptor α (ERα) antagonist is the most common treatment for ERα-positive breast cancer. However, compensatory signaling contributes to resistance to ERα antagonists. Thus, to explore the potential agents for targeting compensatory signaling, we screened multiple target inhibitors for breast cancer treatment. MATERIALS AND METHODS: We attempted to build a structure-based virtual screening model that can find potential compounds and assay the anticancer ability of these drugs by overall cell survival assay. The downstream compensatory phosphorylated signaling was measured by immunoblotting. RESULTS: Hamamelitannin and glucocheirolin were hits for ERα, phosphoinositide 3-kinase (PI3K), and KRAS proto-oncogene, GTPase (KRAS), which were active against estrogen and epidermal growth factor-triggered proliferation. Additionally, we select aminopterin as a hit for ERα, PI3K, KRAS, and SRC proto-oncogene, non-receptor tyrosine kinase (SRC) with inhibitory activities toward AKT serine/threonine kinase 1 (AKT) and mitogen-activated protein kinase kinase (MEK) signaling. CONCLUSION: Our structure-based virtual screening model selected hamamelitannin, glucocheirolin, aminopterin, and pemetrexed as compounds that may act as potential inhibitors for improving endocrine therapies for breast cancer. Copyright
BACKGROUND/AIM: Estrogen receptor α (ERα) antagonist is the most common treatment for ERα-positive breast cancer. However, compensatory signaling contributes to resistance to ERα antagonists. Thus, to explore the potential agents for targeting compensatory signaling, we screened multiple target inhibitors for breast cancer treatment. MATERIALS AND METHODS: We attempted to build a structure-based virtual screening model that can find potential compounds and assay the anticancer ability of these drugs by overall cell survival assay. The downstream compensatory phosphorylated signaling was measured by immunoblotting. RESULTS:Hamamelitannin and glucocheirolin were hits for ERα, phosphoinositide 3-kinase (PI3K), and KRAS proto-oncogene, GTPase (KRAS), which were active against estrogen and epidermal growth factor-triggered proliferation. Additionally, we select aminopterin as a hit for ERα, PI3K, KRAS, and SRC proto-oncogene, non-receptor tyrosine kinase (SRC) with inhibitory activities toward AKT serine/threonine kinase 1 (AKT) and mitogen-activated protein kinase kinase (MEK) signaling. CONCLUSION: Our structure-based virtual screening model selected hamamelitannin, glucocheirolin, aminopterin, and pemetrexed as compounds that may act as potential inhibitors for improving endocrine therapies for breast cancer. Copyright
Authors: Susana Sánchez-Tena; María L Fernández-Cachón; Anna Carreras; M Luisa Mateos-Martín; Noelia Costoya; Mary P Moyer; María J Nuñez; Josep L Torres; Marta Cascante Journal: J Nat Prod Date: 2012-01-04 Impact factor: 4.050