Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells

Abstract

Background

Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity.

Methods

Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells.

Results

The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL (p < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis (p < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells.

Conclusion

Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

HIGHLIGHTS

• Curcumin nanoparticles (Cur-NPs) increase the anticancer efficiency of Curcumin against liver cancer cells.

• Cur-NPs induce apoptotic cell death of Liver cancer cells.

• Cur-NPs have ant-angiogenesis and metastasis effect.

Keywords:

• Curcumin nanoparticles
• liver cancer cells
• migration
• chick embryo angiogenic assay
• proapoptotic pathway

Authors’ contributions

S. Mousa S. Harakeh, SH. Sabre, and ZY. Abd Elmageed; designed and guide the experiments. SH. Sabre, and ZY. Abd Elmageed; did the lab work. T. alamri, R Al-Raddadi, S. Al-Jaouni, H. M. Qari, M. Moulay, and S.Haque: Data visualisation and analysis, wrote the manuscript. All authors agree to the final version of the manuscript.

Consent for publication

All authors have provided consent for the manuscript to be published.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability statement

The data sets used and/or analysed during this study are available from the corresponding author on reasonable request.

Additional information

Funding

This research work was funded by Institutional Fund Projects under grant no (IFPRC-052-248-2020). Therefore, authors gratefully acknowledge technical and financial support from the Ministry of Education and King Abdulaziz University, Jeddah, Saudi Arabia.