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
Author(s) -
Nabilah Muhammad Nadzri,
Ahmad Bustamam Abdul,
Mohd Aspollah Sukari,
Siddig İbrahim Abdelwahab,
Eltayeb E. M. Eid,
Syam Mohan,
Behnam Kamalıdehghan,
Theebaa Anasamy,
Kuan Beng Ng,
Suvitha Syam,
Ismail Adam Arbab,
Heshu Sulaiman Rahman,
Hapipah Mohd Ali
Publication year - 2013
Publication title -
evidence-based complementary and alternative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.552
H-Index - 90
eISSN - 1741-4288
pISSN - 1741-427X
DOI - 10.1155/2013/810632
Subject(s) - apoptosis , cytochrome c , chemistry , caspase 3 , hepatocellular carcinoma , population , cyclodextrin , programmed cell death , mitochondrion , cancer research , biochemistry , microbiology and biotechnology , biology , medicine , environmental health
Zerumbone (ZER) isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl- β -cyclodextrin (HP β CD) to enhance ZER's solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HP β CD 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-HP β CD 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-HP β CD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.
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