NALLA, Lakshmi Vineela and Amit Suresh KHAIRNAR. Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer. Free Radical Biology and Medicine. NEW YORK: ELSEVIER SCIENCE INC, 2024, vol. 220, August 2024, p. 288-300. ISSN 0891-5849. Available from: https://dx.doi.org/10.1016/j.freeradbiomed.2024.05.018.
Other formats:   BibTeX LaTeX RIS
Basic information
Original name Empagliflozin drives ferroptosis in anoikis-resistant cells by activating miR-128-3p dependent pathway and inhibiting CD98hc in breast cancer
Authors NALLA, Lakshmi Vineela and Amit Suresh KHAIRNAR (356 India, belonging to the institution).
Edition Free Radical Biology and Medicine, NEW YORK, ELSEVIER SCIENCE INC, 2024, 0891-5849.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30204 Oncology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 7.400 in 2022
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1016/j.freeradbiomed.2024.05.018
UT WoS 001242109800001
Keywords in English Ferroptosis; Reactive oxygen species; Breast cancer; Metastasis; Anoikis resistance
Tags 14110515, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 1/7/2024 13:41.
Abstract
A tumour suppressor miRNA, miR-128-3p, is widely involved in various biological processes and has been found to get downregulated in breast cancer patients. We previously published that ectopically expressed miR-128-3p suppressed migration, invasion, cell cycle arrest, and breast cancer stem cells. In the present study, we explored the role of Empagliflozin (EMPA) as a miR-128-3p functionality-mimicking drug in inducing ferroptosis by inhibiting CD98hc. Given that CD98hc is one of the proteins critical in triggering ferroptosis, we confirmed that miR-128-3p and EMPA inhibited SP1, leading to inhibition of CD98hc expression. Further, transfection with siCD98hc, miR-128-3p mimics, and inhibitors was performed to assess their involvement in the ferroptosis of anoikis-resistant cells. We proved that anoikis-resistant cells possess high ROS and iron levels. Further, miR-1283p and EMPA treatments induced ferroptosis by inhibiting GSH and enzymatic activity of GPX4 and also induced lipid peroxidation. Moreover, EMPA suppressed bioluminescence of 4T1-Red-FLuc induced thoracic cavity, peritoneal tumour burden and lung nodules in an in-vivo metastatic model of breast cancer. Collectively, we revealed that EMPA sensitized the ECM detached cells to ferroptosis by synergically activating miR-128-3p and lowering the levels of SP1 and CD98hc, making it a potential adjunct drug for breast cancer chemotherapy.
Links
LX22NPO5107, research and development projectName: Národní ústav pro neurologický výzkum
Investor: Ministry of Education, Youth and Sports of the CR, 5.1 EXCELES
PrintDisplayed: 19/7/2024 15:28