File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Melatonin and erastin emerge synergistic anti-tumor effects on oral squamous cell carcinoma by inducing apoptosis, ferroptosis, and inhibiting autophagy through promoting ROS

TitleMelatonin and erastin emerge synergistic anti-tumor effects on oral squamous cell carcinoma by inducing apoptosis, ferroptosis, and inhibiting autophagy through promoting ROS
Authors
KeywordsApoptosis
Autophagy
Erastin
Ferroptosis
Melatonin
Oral cancer
Reactive oxygen species (ROS)
Issue Date2-May-2023
PublisherBioMed Central
Citation
Cellular & Molecular Biology Letters, 2023, v. 28, n. 1 How to Cite?
Abstract

Background

Oral squamous cell carcinomas are one of the most common cancers worldwide with aggressive behavior and poor prognosis. Reactive oxygen species (ROS) are associated with cancer and cause various types of regulated cell death (RCD). Inducing the RCD pathway by modulating ROS levels is imperative to conquer cancers. The aim of this study is to investigate the synergistic anticancer effects of melatonin and erastin on ROS modulation and subsequent RCD induction.

Methods

Human tongue squamous cell carcinoma cell lines (SCC-15 cells) were treated with melatonin, erastin, or their combination. Cell viability, ROS levels, autophagy, apoptosis, and ferroptosis levels were tested according to the results of the PCR array, which were verified with/without the induction and inhibition of ROS by H2O2 and N-acetyl-L-cysteine, respectively. In addition, a mouse-based subcutaneous oral cancer xenograft model was constructed to identify the effects of melatonin, erastin, and their combination on the autophagy, apoptosis, and ferroptosis levels in isolated tumor tissues.

Results

ROS levels were increased by the administration of melatonin at high concentrations (mM), and the combination of melatonin with erastin enhanced the levels of malonic dialdehyde, ROS, and lipid ROS, and reduced the levels of glutamate and glutathione. SQSTM1/p62, LC3A/B, cleaved caspase-3, and PARP1 protein levels in SCC-15 cells were also increased by melatonin plus erastin treatment, which further increased as ROS accumulated, and decreased as ROS levels were suppressed. Combined treatment of melatonin and erastin markedly reduced the tumor size in vivo, demonstrated no obvious systemic side effects, and significantly enhanced the apoptosis and ferroptosis levels in the tumor tissues, in parallel with decreased autophagy levels.

Conclusions

Melatonin combined with erastin exhibits synergistic anticancer effects without adverse reactions. Herein, this combination might become a promising alternative strategy for oral cancer treatment.


Persistent Identifierhttp://hdl.handle.net/10722/331512
ISSN
2023 Impact Factor: 9.2
2023 SCImago Journal Rankings: 2.229
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Leilei-
dc.contributor.authorWang, Chuan-
dc.contributor.authorLi, Xuan-
dc.contributor.authorTao, Zhuoying-
dc.contributor.authorZhu, Wangyong-
dc.contributor.authorSu, Yuxiong-
dc.contributor.authorChoi, Wing Shan-
dc.date.accessioned2023-09-21T06:56:30Z-
dc.date.available2023-09-21T06:56:30Z-
dc.date.issued2023-05-02-
dc.identifier.citationCellular & Molecular Biology Letters, 2023, v. 28, n. 1-
dc.identifier.issn1425-8153-
dc.identifier.urihttp://hdl.handle.net/10722/331512-
dc.description.abstract<h3>Background</h3><p>Oral squamous cell carcinomas are one of the most common cancers worldwide with aggressive behavior and poor prognosis. Reactive oxygen species (ROS) are associated with cancer and cause various types of regulated cell death (RCD). Inducing the RCD pathway by modulating ROS levels is imperative to conquer cancers. The aim of this study is to investigate the synergistic anticancer effects of melatonin and erastin on ROS modulation and subsequent RCD induction.</p><h3>Methods</h3><p>Human tongue squamous cell carcinoma cell lines (SCC-15 cells) were treated with melatonin, erastin, or their combination. Cell viability, ROS levels, autophagy, apoptosis, and ferroptosis levels were tested according to the results of the PCR array, which were verified with/without the induction and inhibition of ROS by H<sub>2</sub>O<sub>2</sub> and N-acetyl-L-cysteine, respectively. In addition, a mouse-based subcutaneous oral cancer xenograft model was constructed to identify the effects of melatonin, erastin, and their combination on the autophagy, apoptosis, and ferroptosis levels in isolated tumor tissues.</p><h3>Results</h3><p>ROS levels were increased by the administration of melatonin at high concentrations (mM), and the combination of melatonin with erastin enhanced the levels of malonic dialdehyde, ROS, and lipid ROS, and reduced the levels of glutamate and glutathione. SQSTM1/p62, LC3A/B, cleaved caspase-3, and PARP1 protein levels in SCC-15 cells were also increased by melatonin plus erastin treatment, which further increased as ROS accumulated, and decreased as ROS levels were suppressed. Combined treatment of melatonin and erastin markedly reduced the tumor size in vivo, demonstrated no obvious systemic side effects, and significantly enhanced the apoptosis and ferroptosis levels in the tumor tissues, in parallel with decreased autophagy levels.</p><h3>Conclusions</h3><p>Melatonin combined with erastin exhibits synergistic anticancer effects without adverse reactions. Herein, this combination might become a promising alternative strategy for oral cancer treatment.</p>-
dc.languageeng-
dc.publisherBioMed Central-
dc.relation.ispartofCellular & Molecular Biology Letters-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectApoptosis-
dc.subjectAutophagy-
dc.subjectErastin-
dc.subjectFerroptosis-
dc.subjectMelatonin-
dc.subjectOral cancer-
dc.subjectReactive oxygen species (ROS)-
dc.titleMelatonin and erastin emerge synergistic anti-tumor effects on oral squamous cell carcinoma by inducing apoptosis, ferroptosis, and inhibiting autophagy through promoting ROS-
dc.typeArticle-
dc.identifier.doi10.1186/s11658-023-00449-6-
dc.identifier.scopuseid_2-s2.0-85157966482-
dc.identifier.volume28-
dc.identifier.issue1-
dc.identifier.eissn1689-1392-
dc.identifier.isiWOS:000981587700001-
dc.identifier.issnl1425-8153-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats