Curcumin-loaded liposomes modulating the synergistic role of EpCAM and estrogen receptor alpha in lung cancer management

Manisha Singh; Gabriele De Rubis; Sofia Kokkinis; Keshav Raj Paudel; Stewart Yeung; Philip Michael Hansbro; Brian Gregory George Oliver; Kamal Dua

doi:10.1016/j.prp.2024.155317

Curcumin-loaded liposomes modulating the synergistic role of EpCAM and estrogen receptor alpha in lung cancer management

Pathol Res Pract. 2024 May:257:155317. doi: 10.1016/j.prp.2024.155317. Epub 2024 Apr 17.

Authors

Manisha Singh¹, Gabriele De Rubis², Sofia Kokkinis³, Keshav Raj Paudel⁴, Stewart Yeung⁵, Philip Michael Hansbro⁴, Brian Gregory George Oliver⁶, Kamal Dua⁷

Affiliations

¹ Department of Biotechnology, Jaypee Institute of Information Technology (JIIT) Noida, Uttar Pradesh, India; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.
² Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia.
³ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia; Pharmako Biotechnologies, Sydney, NSW 2086, Australia.
⁴ Centre of Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2007, Australia.
⁵ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.
⁶ Woolcock Institute of Medical Research, Macquarie University, New South Wales, Australia; School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
⁷ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia. Electronic address: kamal.dua@uts.edu.au.

PMID: 38657558
DOI: 10.1016/j.prp.2024.155317

Abstract

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration of innovative therapeutic strategies. This study delves into the in vitro potential of liposomal therapeutics utilizing Curcumin-loaded PlexoZome® (CUR-PLXZ) in targeting EpCAM/TROP1 and Estrogen Receptor Alpha (ERα) signalling pathways for LC management. The prevalence of LC, particularly non-small cell lung cancer (NSCLC), underscores the urgent need for effective treatments. Biomarkers like EpCAM/TROP1 and ERα/NR3A1 play crucial roles in guiding targeted therapies and influencing prognosis. EpCAM plays a key role in cell-cell adhesion and signalling along with ERα which is a nuclear receptor that binds estrogen and regulates gene expression in response to hormonal signals. In LC, both often get overexpressed and are associated with tumour progression, metastasis, and poor prognosis. Curcumin, a phytochemical with diverse therapeutic properties, holds promise in targeting these pathways. However, its limited solubility and bioavailability necessitate advanced formulations like CUR-PLXZ. Our study investigates the biological significance of these biomarkers in the A549 cell line and explores the therapeutic potential of CUR-PLXZ, which modulates the expression of these two markers. An in vitro analysis of the A549 human lung adenocarcinoma cell line identified that CUR-PLXZ at a dose of 5 μM effectively inhibited the expression of EpCAM and ERα. This finding paves the way for targeted intervention strategies in LC management.

Keywords: Curcumin; Liposomes; Lung Cancer; Phytoceuticals; Respiratory Diseases.

MeSH terms

A549 Cells
Antineoplastic Agents / pharmacology
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / pathology
Curcumin* / pharmacology
Epithelial Cell Adhesion Molecule* / metabolism
Estrogen Receptor alpha* / metabolism
Humans
Liposomes*
Lung Neoplasms* / drug therapy
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology

Substances

Epithelial Cell Adhesion Molecule
Curcumin
Estrogen Receptor alpha
Liposomes
EPCAM protein, human
ESR1 protein, human
Antineoplastic Agents