Abu Bakar, Mohd Fadzelly
(2010)
Chemopreventive and chemotherapeutic properties of selected fruits endemic to Borneo: investigation on Mangifera pajang and Artocarpus odoratissimus.
PhD thesis, University of Nottingham.
Abstract
Consumption of fruits and vegetables has been shown to reduce the risk of various types of cancer. Macro- and micro-nutrients as well as non-nutritive phytochemicals present in fruits and vegetables have been associated with this effect. This study was conducted to investigate the chemopreventive and chemotherapeutic potential of two types of fruits which are endemic to Borneo Island: Mangifera pajang (bambangan) and Artocarpus odoratissimus (tarap).
The first part of the project was to study the antioxidant potential of the crude extracts of the plants in vitro. The fruits were first separated into flesh, kernel and peel for M. pajang and flesh and seed for A. odoratissmus. DPPH (2,2- diphenyl-I-picrylhydrazyl) free radical scavenging and FRAP (ferric reducing / antioxidant power) assay were employed for the antioxidant study. The result showed that the kernel of M. pajang extract displayed strongest antioxidant activity as assessed using both assays, followed by M. pajang peel, A. odoratissmus seed, M. pajang flesh and A. odoratissmus flesh.
The presence of selected phytochemicals in the plant extracts was determined in the next chapter. Polyphenols have been identified as major phytochemicals in the plant extracts, and in M. pajang kernel extract represents about 10% of its total weight. Gallic acid, coumaric acid, sinapic acid, caffeic acid, ferulic acid, chlorogenic acid, naringin, hesperidin, rutin, luteolin and diosmin have been identified as the key polyphenol phytochemicals present in the kernel of M. pajang which might be responsible for the superior antioxidant properties as compared to other extracts.
Concern that the results for the chemical antioxidant assay do not necessarily reflect cellular activity led to the third part of the project; assessment of the cytoprotective activity of the crude extracts against oxidative stress induced by tert-butyl hydroperoxide (t-BHP). Only M. pajang kernel extract as well as the positive control (quercetin) displayed cytoprotective activity against this toxicant. It seems that non-cell based antioxidant assay does not necessarily reflect the activity in cell-based antioxidant assay. This is shown by lack of cytoprotective activity of both M. pajang peel and A. odoratissimus extracts despite their considerably high antioxidant activity in DPPH free radical scavenging and FRAP assay.
In order to study which proteins might be involved in the cytoprotection mechanism, western blotting method was employed to determine the expression of various Cytoprotective proteins [i.e. quinone reductase (NQO I), glutathione peroxidase (OR), methionine sulfoxide reductase A (MSRA), heat shock protein 27 (HSP27) and heat shock protein 70 (HSP 70)]. Different cytoprotective mechanisms were observed by the kernel extracts and quercetin. In the present study, NQOI, OR, MSRA, HSP27 and HSP 70 have been shown to be involved in the cytoprotection activity of quercetin while only OR and MSRA were involved in the cytoprotection activity of M. pajang kernel extracts. Other cytoprotective proteins remain to be studied to fully understand the cytoprotection mechanism of both plant extract and quercetin.
Some chemopreventive agents have been shown to suppress cancer proliferation, induce apoptosis in cancer cells as well as inhibit angiogenesis and metastasis in pre-clinical and clinical trials. Thus, the last part of the project was to determine the anti-cancer potential of plant extracts in a variety of cancer cell lines (derived from breast, colon, liver and ovarian carcinoma). The results showed that the kernel extract of M. pajang displayed strong anti proliferative activity in breast cancer cell lines (MCF-7 and MDA-MB-231). The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24 hours, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72 hours of incubation. Staining with Annexin V -FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36 hours for MCF-7 cells and 24 hours for MDA-MB- 231 cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspases-2 and -3 in MCF-7 cells and on caspases-2, -3 and -9 in MDA-MB-231 cells.
As a conclusion, from the two plants (M. pajang and A. odoratissimus) studied, the extract of M. pajang kernel displayed diverse health benefit properties, antioxidant, chemoprevention and chemotherapeutic potential. M. pajang could be fully utilized for pharmaceutical, nutraceutical as well as food products. Further study (i.e. animal and clinical study, isolation of pure compounds, bioavailability study) are required to determine the efficacy in human population.
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