Investigation of the apoptotic effects of cycloart-24-ene-36β,26-diol from Aglaia exima on selected breast cancer cell lines / Deepa Jeevananthan

• Main Author: Deepa, Jeevananthan
• Format: Thesis
• Published: 2018
• Subjects: R Medicine (General); RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Online Access: http://studentsrepo.um.edu.my/11567/4/deepa.pdf; http://studentsrepo.um.edu.my/11567/

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.