Green-synthesized copper oxide nanoparticles induce apoptosis and up-regulate HOTAIR and HOTTIP in pancreatic cancer cells

Abstract

Aim: Cu₂O nanoparticles were synthesized using an extract from S. latifolium algae (SLCu₂O NPs). Their effect on PANC-1 cells and the expression of two drug resistance-related lncRNAs were evaluated in comparison with Arsenic trioxide. Materials & methods: SLCu₂O NPs were characterized using XRD, SEM, and TEM microscopies. The effects of SLCu₂O NPs on cell cytotoxicity, cell cycle, and apoptosis, and expression of two drug resistance-related lncRNAs were examined using MTT assay, flow cytometry, and real-time PCR, respectively. Results: SLCu₂O NPs demonstrated anti-cancer properties against PANC-1 cells comparable to Arsenic trioxide, and the expression of lncRNAs increased upon treatment with them. Conclusion: SLCu₂O NPs demonstrate anti-cancer properties against PANC-1 cells; however, using gene silencing strategies along with SLCu₂O NPs is suggested.

Article highlights

• Copper nanoparticles have been proposed as a novel anti-cancer agent in cancer research including Pancreatic cancer.

• Copper oxide nanoparticles synthesis via physicochemical routs restricted their use in further cancer research or future clinical applications due to using highly toxic chemicals, high energy consumption, and high cost of synthesis.

• In this study, Cu₂O nanoparticles were synthesized using an extract from S. latifolium algae to address environmental concerns.

• The XRD patterns of the S. latifolium-derived Cu₂O nanoparticles showed the prominent peaks attributed to planes (110), (111), (200), (220), (311), and (222) that confirm the formation of the single-phase cubic structure with Pn-3m space group.

• Scanning electron microscopy confirm the spherical-cubic shape of S. latifolium-derived Cu₂O nanoparticles with the average size of 40–50 nm.

• S. latifolium-derived Cu₂O nanoparticles induced cell cytotoxicity on PANC-1 cells with IC₅₀ of 72.75 and 65.4 μg/ml at 24 and 48 h, respectively.

• S. latifolium-derived Cu₂O nanoparticles induced S-phase cell cycle arrest and apoptosis in PANC-1 cells.

• S. latifolium-derived Cu₂O nanoparticles showed comparable effects to arsenic trioxide in terms of cell cytotoxicity, colony formation, cell cycle arrest, and apoptosis.

• S. latifolium-derived Cu₂O nanoparticles increased the expression of two drug-resistant related lncRNAs, HOTAIR and HOTTIP, which may suggest using gene silencing strategies along with these nanoparticles.

Keywords: :

• algae
• arsenic trioxide
• chemoresistance
• copper
• long non-coding RNA

Acknowledgments

The authors are grateful to the research management of the Persian Gulf University for providing this research opportunity.

Author contributions

Z Hosseini participated in data curation, formal analysis, and writing- original draft preparation. A Shadi, SJ Hosseini and H Nikmanesh contributed to conceptualization, review and editing. A Ahmadi contributed to the supervision of the study, data validation, writing-review and editing of the manuscript.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.