Date of Award

1-1-2018

Thesis Type

masters

Document Type

Thesis

Divisions

medic

Department

Faculty of Medicine

Institution

University of Malaya

Abstract

The main purpose of this study is to investigate the cytotoxic potential and anticancer mechanism of cycloart-24-ene-3β,26-diol isolated from the leaves of Aglaia exima of the Meliaceae family through a bioassay-guided fractionation. In vitro assays of this compound were conducted on two cancer cell lines—hormone-dependent breast adenocarcinoma cells (MCF-7) and hormone-independent breast adenocarcinoma cells (MDA-MB-231) in comparison with the normal human mammary epithelial cell line (hTERT-HME1). Cell viability was assessed using the MTS (3-[4,5-dimethylthiazol-2- yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulphophenyl]-2H-tetrazolium, inner salt) assay. Flow cytometry analysis was used to determine the mode of cell death and cell cycle arrest caused by the compound. Caspase 3/7 assay was performed to investigate caspase activation, while aromatase inhibitory activity was examined using the CYP19-MFC assay. The results showed that cycloart-24-ene-3β,26-diol is cytotoxic to MCF-7 and MDA-MB-231 in a dose- and time-dependent manner. Conversely, cycloart-24-ene3β,26-diol did not significantly affect the viability of normal mammary cells within a similar concentration range. Flow cytometric analysis of annexin V/propidium iodide (PI) dual staining showed that cell death was through apoptosis. The apoptotic effects was further confirmed by caspase 3/7 activation. Cell cycle analysis showed that cycloart-24-ene-3β,26-diol caused G1-S phase arrest in MCF-7. Besides, we found that cycloart-24-ene-3β,26-diol inhibited CYP19 (aromatase), suggesting a potential aromatase inhibitor. In conclusion, cycloart-24-ene-3β,26-diol, a natural compound from the leaves of Aglaia exima may have the potential to be further developed into a chemopreventive agent for breast cancer.

Note

Dissertation (M.A.) – Faculty of Medicine, University of Malaya, 2018.

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