RT Journal Article
SR Electronic
T1 Drug Screening of Potential Multiple Target Inhibitors for Estrogen Receptor-α-positive Breast Cancer
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 761
OP 777
DO 10.21873/invivo.12317
VO 35
IS 2
A1 YUN-HAO DAI
A1 GUAN-YU CHEN
A1 CHIH-HSIN TANG
A1 WEI-CHIEN HUANG
A1 JUAN-CHENG YANG
A1 YANG-CHANG WU
YR 2021
UL http://iv.iiarjournals.org/content/35/2/761.abstract
AB 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.