Diallyl trisulfide inhibits osteosarcoma 143B cell migration, invasion and EMT by inducing autophagy

Xiyu Liu; Nan Wang; Zhiwei He; Chen Chen; Jun Ma; Xin Liu; Shan Deng; Lin Xie

doi:10.1016/j.heliyon.2024.e26681

Diallyl trisulfide inhibits osteosarcoma 143B cell migration, invasion and EMT by inducing autophagy

Heliyon. 2024 Feb 22;10(5):e26681. doi: 10.1016/j.heliyon.2024.e26681. eCollection 2024 Mar 15.

Authors

Xiyu Liu¹, Nan Wang¹, Zhiwei He¹, Chen Chen², Jun Ma³, Xin Liu¹, Shan Deng¹, Lin Xie¹

Affiliations

¹ The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
² Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng City, China.
³ Huai'an TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Huai'an, China.

Abstract

Background: Diallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway.

Methods: In this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 μM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers.

Results: DATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells.

Conclusions: This study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.

Keywords: Autophagy; Diallyl trisulfide; EGFR/PI3K/AKT/mTOR; Osteosarcoma.