Abu Bakar, Siti Aishah (2023) Study Of Goniothalamin And Bioactive Glass 45s5 (Gtn-bg) On Osteosarcoma Saos-2 And Breast Adenocarcinoma Mcf-7 Cells. PhD thesis, Universiti Sains Malaysia.
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Abstract
Developing alternative cancer treatment is crucial due to the limitations of conventional chemotherapy, which can harm healthy cells while targeting cancer cells. Plant-derived natural products, with their diverse mechanisms and low toxicity, hold promise as cancer treatments, and their combination with bioactive materials may improve treatment effectiveness. In this study, the cytotoxic activity of a plant styryl lactone, goniothalamin (GTN) was screened first in several human cancer cell lines and was found to possess a substantial range of cytotoxicity against osteosarcoma (Saos-2), breast adenocarcinoma (MCF-7), breast carcinoma (UACC-732), adenocarcinoma alveolar basal epithelial (A549) and colorectal adenocarcinoma (HT29) cells, but less toxicity towards human bone marrow-derived mesenchymal stem (HMSC) cells. GTN demonstrated selective toxicity towards cancer cells with a high SI value (>2) for each examined cancer cell line compared to doxorubicin (DOX). The potential enhancement of GTN's anticancer effects was explored by combining it with a sol-gel-derived bioactive glass 45S5 (BG 45S5) that possesses bioactive, biocompatible, and biodegradable properties. The combination of GTN-BG was found more potent than GTN in inhibiting the proliferation of Saos-2 and MCF-7 cells due to a better microenvironment provided with the release of ionic dissolution products such as Ca2+, Na+ and Mg2+ ions from the BG. For both GTN and GTN-BG treatments, several apoptotic features were detected when observed under a phase microscope, including cell shrinkage, rounded cells, and membrane blebbing. It was found that apoptosis was triggered through the extrinsic death receptor pathway as the activation of caspase 8 was mainly detected and significantly higher in GTN-BG compared to GTN. The binding of a death ligand triggers the activation of caspase 8, which later activates the effector’s caspase 3/7. These results were supported by transcriptome profiling. Several TNFRSF members, including TNFRSF1A, TNFRSF16, and TNFRSF14 genes, were upregulated in Saos-2 cells treated with GTN-BG. GTN-BG treatment also induced the expression of DUSP4, DUSP6, PLK5 and CHOP genes that may contribute to cell cycle arrest at the G2/M phase, subsequently resulted in apoptosis. To conclude, the antiproliferative and apoptotic activities of GTN were enhanced with the combination of BG.
| Item Type: | Thesis (PhD) |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Institut Perubatan & Pergigian Termaju (Advanced Medical & Dental Institute (AMDI)) > Thesis |
| Depositing User: | MUHAMAD AMIN BIN AZMI |
| Date Deposited: | 25 Feb 2026 01:05 |
| Last Modified: | 25 Feb 2026 01:05 |
| URI: | http://eprints.usm.my/id/eprint/63647 |
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