Affiliations 

  • 1 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, 2007, Australia
  • 2 Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2050, Australia
  • 3 School of Postgraduate Studies, International Medical University (IMU), 57000, Kuala Lumpur, Malaysia
  • 4 Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, 57000, Kuala Lumpur, Malaysia
  • 5 Departamento de Química Orgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, 7820436, Macul, Santiago, Chile
  • 6 School of Biomedical Engineering, University of Technology Sydney, Sydney, New South Wales, Australia
  • 7 Research and Development, Aerogen Limited, IDA Business Park, Galway, Connacht, H91 HE94, Ireland
  • 8 Woolcock Institute of Medical Research, Macquarie University, Sydney, NSW, 2137, Australia
  • 9 School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan, India
  • 10 Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Sydney, NSW, 2007, Australia
  • 11 Department of Life Sciences, School of Pharmacy, International Medical University, 57000, Kuala Lumpur, Malaysia. dinesh_kumar@imu.edu.my
  • 12 Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2050, Australia. philip.hansbro@uts.edu.au
  • 13 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, 2007, Australia. kamal.dua@uts.edu.au
Naunyn Schmiedebergs Arch Pharmacol, 2024 Jan;397(1):343-356.
PMID: 37439806 DOI: 10.1007/s00210-023-02603-5

Abstract

Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.