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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 810632, 16 pages
http://dx.doi.org/10.1155/2013/810632
Research Article

Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

1UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia (UPM), Serdang, 43400 Selangor, Malaysia
2Department of Chemistry, Faculty of Science, University Putra Malaysia (UPM), Serdang, 43400 Selangor, Malaysia
3Department of Pharmacy, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, Malaysia
4Medical Research Center, Faculty of Medicine, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia
5College of Pharmacy, Qassim University, P.O. Box 2055, Buraydah 6800, Saudi Arabia
6Department of Microbiology and Pathology, Faculty of Veterinary Medicine, University Putra Malaysia (UPM), Serdang, 43400 Selangor, Malaysia
7Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

Received 10 January 2013; Accepted 3 April 2013

Academic Editor: Gail B. Mahady

Copyright © 2013 Nabilah Muhammad Nadzri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Zerumbone (ZER) isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD) to enhance ZER’s solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.