Research Paper Volume 13, Issue 8 pp 11026—11042
Calycosin stimulates the proliferation of endothelial cells, but not breast cancer cells, via a feedback loop involving RP11-65M17.3, BRIP1 and ERα
- 1 Key Laboratory of Tumor Immunology and Microenvironmental Regulation of Guangxi, Guilin Medical University, Guilin 541004, Guangxi, China
- 2 Department of Physiology, Guilin Medical University, Guilin 541004, Guangxi, China
- 3 Department of Breast and Thyroid Surgery, First Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China
Received: July 17, 2020 Accepted: November 3, 2020 Published: March 1, 2021https://doi.org/10.18632/aging.202641
How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
It is widely accepted that estrogen can be replaced by phytoestrogens to treat postmenopausal cardiovascular disease and possibly decrease the risk of breast cancer. However, few studies have investigated the effects of phytoestrogens on vascular endothelial cells (ECs). In the present study, we show that the phytoestrogen calycosin (20 μM) stimulated the proliferation of ECs (HUVECs and HMEC-1) but inhibited the growth of breast cancer cells (BCCs) expressing ERα (MCF-7 and T47D). Here we provide evidence for the presence of a positive feedback loop between ERα and long noncoding RNA RP11-65M17.3 in both normal and cancer cells, and calycosin stimulated this feedback loop in ECs but decreased RP11-65M17.3 expression in BCCs. Subsequently, the calycosin-induced activation of this loop decreased the expression of the target of BRIP1 (BRCA1 interacting protein C-terminal helicase 1), increased the phosphorylation of Akt and ERK1/2, and finally inhibited the cleavage of PARP-1 in ECs. In nude mice bearing MCF-7 xenografts, calycosin did not stimulate tumor growth as strongly as 17β-estradiol. Together, these results suggest that calycosin promotes the proliferation of ECs, and notable inhibits the growth of BCCs. A possible reason for these results is the involvement of a feedback loop between ERα and RP11-65M17.3.