Valtrate antagonizes malignant phenotypes of lung cancer cells by reducing SLC7A11.

Abstract

OBJECTIVES:

This research explored the efficacy of valtrate (Val) in lung cancer (LC).

METHODS:

A549 and H1299 cells were dealt with Val. SLC7A11 was overexpressed by cell transfection. Xenograft model was established in nude mice. Cell viability, proliferation and apoptosis were measured by CCK-8, EdU and Annexin-V and propidium iodide staining, respectively. Ferroptosis was assessed by iron assay kit. reactive oxygen species level was tested by ROS assay kit. Histopathological changes in tumor tissues were analyzed by HE staining. Protein expression was analyzed employing Immunohistochemical staining and western blot.

RESULTS:

A549 and H1299 cell viability were notably lowered by Val in a concentration-dependent way. Cell proliferation was markedly repressed by 10 and 20 μM of Val, while apoptosis and ROS generation were markedly augmented. SLC7A11 and GPX4 expression was both distinctly lowered, while Fe2+ level was remarkably improved by 10 and 20 μM of Val. However, 20 μM of Val-triggered effects were distinctly counteracted by SLC7A11 overexpression. In vivo assay revealed that both tumor volume and weight were distinctly declined by 10 mg/mL Val. The variations of proliferation, apoptosis and ferroptosis-related proteins were in line with the results in vitro assay.

CONCLUSION:

Val might antagonize malignant phenotypes of LC cells by reducing SLC7A11.

• Authors: Wei Xu, Huan Yu
• Journal: Human & experimental toxicology (Hum Exp Toxicol) 2022 Jan-Dec Vol. 41 Pg. 9603271221124096 ISSN: 1477-0903 [Electronic] England
• PMID: 36048842 (Publication Type: Journal Article)

Chemical References

• Amino Acid Transport System y+
• Iridoids
• Reactive Oxygen Species
• SLC7A11 protein, human
• valtrate

Topics

• Amino Acid Transport System y+ (genetics, metabolism)
• Animals
• Humans
• Iridoids
• Lung Neoplasms (metabolism)
• Mice
• Mice, Nude
• Phenotype
• Reactive Oxygen Species (metabolism)