Antiproliferative effects of zerumbone-hydroxypropyl-ß-cyclodextrin inclusion complex on HepG2 liver cancer cells in vitro
Zingiber zerumbet Smith locally known as ‘lempoyang’ or wild ginger belongs to the Zingiberaceae family. Previous investigations on Z. zerumbet proved that it contained a bioactive compound, zerumbone (ZER), a crystalline sesquiterpene possessing suppressive effect in cancers. The purpose of e...
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| Format: | Thesis |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/67614/1/IB%202013%2035%20IR.pdf |
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| Summary: | Zingiber zerumbet Smith locally known as ‘lempoyang’ or wild ginger belongs to the
Zingiberaceae family. Previous investigations on Z. zerumbet proved that it
contained a bioactive compound, zerumbone (ZER), a crystalline sesquiterpene
possessing suppressive effect in cancers. The purpose of encapsulating ZER with
hydroxylpropyl-β-cyclodextrin (HPβCD) is to modify ZER’s solubility and
pharmacokinetic properties making it less harmful to the human body. The objective
of this study is to investigate antiproliferative activities of ZER-HPβCD inclusion
complex towards HepG2 liver cancer cells. The MTT assay showed that the
inclusion complex is cytotoxic towards HepG2 cells with an IC50 of 11.43 μg/ml.
Morphological evaluation showed structural changes associated with apoptosis
including membrane blebbing, cell shrinkage and chromatin condensation. HepG2
cells treated with the inclusion complex further resulted in cell cycle arrest at G2/M
phase with increments of apoptotic cells. 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 pro-apoptotic
and anti-apototic Bcl-2 family members with no significant change of p53. The
activated Bax will be translocated to the mitochondria, which activates the
transformation of mitochondrial function and release of cytochrome c. Upregulation
of caspase 3/7, caspase 9 and caspase 8 were also detected with the depletion of BID
cleaved by caspase 8 proving that both extrinsic and instrinsic pathway were
involved upon ZER-HPβCD induction. Collectively, these results demonstrate that
the highly soluble inclusion complex of ZER with HPβCD induce apoptosis
programmed cell death in HepG2 cells and can be extrapolated to postulate that
caspase 8’s activation is indirectly involved as an interconnection between the
extrinsic and intrinsic pathway. Further investigations to this complex are needed to
substantiate its use as an anticancer against hepatocellular carcinoma in humans. |
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