Allicin promotes autophagy and ferroptosis in esophageal squamous cell carcinoma by activating AMPK/mTOR signaling

Zhanfang Guo; Yanjiao Zhang

doi:10.1016/j.heliyon.2022.e11005

Allicin promotes autophagy and ferroptosis in esophageal squamous cell carcinoma by activating AMPK/mTOR signaling

Heliyon. 2022 Oct 12;8(10):e11005. doi: 10.1016/j.heliyon.2022.e11005. eCollection 2022 Oct.

Authors

Zhanfang Guo¹, Yanjiao Zhang²

Affiliations

¹ Department of Gastroenterology, Dalian Municipal Central Hospital, No. 826, Southwest Road, Hekou District, Dalian City, 116023, Liaoning Province, China.
² The Third Department of Cadres, 967 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, No. 80 Shengli Road, Xigang District, Dalian, 116000, Liaoning Province, China.

Abstract

The antitumor effects of allicin have been demonstrated in various cancers. However, whether allicin improves esophageal squamous cell carcinoma (ESCC) has not yet been explored. The present study aimed to explore the function and underlying mechanism of action of allicin in ESCC treatment. Our data showed that allicin significantly suppressed ESCC cell proliferation in a dose- and time-dependent manner. A green fluorescent protein-light chain 3 (LC3) transfection assay showed that autophagosomes were elevated in ESCC cells treated with allicin compared with control ESCC cells and that 3-methyladenine (an autophagy inhibitor) reversed allicin-induced LC3 puncta. Furthermore, allicin significantly elevated the ratio of LC3II/LC3I but decreased p62 expression in ESCC cells. Allicin also increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation but decreased that of the mechanistic target of rapamycin kinase (mTOR), which then induced the elevation of autophagy-related 5 and autophagy-related 7 proteins in ESCC cells. Furthermore, allicin treatment increased the expression of nuclear receptor coactivator 4 (a selective cargo receptor) but suppressed the expression of ferritin heavy chain 1 (the major intracellular iron-storage protein) in ESCC cells and elevated malondialdehyde and Fe²⁺ production levels. In vivo assays showed that allicin significantly decreased tumor weight and volume. In summary, allicin may induce cell death in ESCC cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Therefore, allicin may have excellent potential for use in the treatment of ESCC.

Keywords: AMPK/mTOR signaling; Autophagy; Esophageal squamous cell carcinoma; Ferroptosis.

Publication types

Retracted Publication